Integrated medicament delivery device for use with continuous analyte sensor

ABSTRACT

An integrated system for the monitoring and treating diabetes is provided, including an integrated receiver/hand-held medicament injection pen, including electronics, for use with a continuous glucose sensor. In some embodiments, the receiver is configured to receive continuous glucose sensor data, to calculate a medicament therapy (e.g., via the integrated system electronics) and to automatically set a bolus dose of the integrated hand-held medicament injection pen, whereby the user can manually inject the bolus dose of medicament into the host. In some embodiments, the integrated receiver and hand-held medicament injection pen are integrally formed, while in other embodiments they are detachably connected and communicated via mutually engaging electrical contacts and/or via wireless communication.

INCORPORATION BY REFERENCE TO RELATED APPLICATIONS

Any and all priority claims identified in the Application Data Sheet, orany correction thereto, are hereby incorporated by reference under 37CFR 1.57. This application is a continuation of U.S. application Ser.No. 14/300,137, filed Jun. 9, 2014, which is a continuation of U.S.application Ser. No. 12/133,820 filed Jun. 5, 2008, now U.S. Pat. No.8,808,228, which is a continuation-in-part of U.S. application Ser. No.10/789,359 filed Feb. 26, 2004, now U.S. Pat. No. 7,591,801. U.S.application Ser. No. 12/133,820 claims the benefit of U.S. ProvisionalApplication No. 60/942,787 filed Jun. 8, 2007. Each of theaforementioned applications is incorporated by reference herein in itsentirety, and each is hereby expressly made a part of thisspecification.

FIELD OF THE INVENTION

The present invention relates generally to systems and methodsmonitoring glucose in a host. More particularly, the present inventionrelates to an integrated medicament delivery device and continuousglucose sensor.

BACKGROUND OF THE INVENTION

Diabetes mellitus is a disorder in which the pancreas cannot createsufficient insulin (Type I or insulin dependent) and/or in which insulinis not effective (Type 2 or non-insulin dependent). In the diabeticstate, the victim suffers from high blood sugar, which can cause anarray of physiological derangements (for example, kidney failure, skinulcers, or bleeding into the vitreous of the eye) associated with thedeterioration of small blood vessels. A hypoglycemic reaction (low bloodsugar) can be induced by an inadvertent overdose of insulin, or after anormal dose of insulin or glucose-lowering agent accompanied byextraordinary exercise or insufficient food intake.

Conventionally, a diabetic person carries a self-monitoring bloodglucose (SMBG) monitor, which typically comprises uncomfortable fingerpricking methods. Due to the lack of comfort and convenience, a diabeticwill normally only measures his or her glucose level two to four timesper day. Unfortunately, these time intervals are so far spread apartthat the diabetic will likely find out too late, sometimes incurringdangerous side effects, of a hyper- or hypo-glycemic condition. In fact,it is not only unlikely that a diabetic will take a timely SMBG value,but the diabetic will not know if their blood glucose value is going up(higher) or down (lower) based on conventional methods, inhibiting theirability to make educated insulin therapy decisions.

Home diabetes therapy requires personal discipline of the user,appropriate education from a doctor, proactive behavior undersometimes-adverse situations, patient calculations to determineappropriate therapy decisions, including types and amounts ofadministration of insulin and glucose into his or her system, and issubject to human error. Technologies are needed that ease the burdensfaced by diabetic patients, simplify the processes involved in treatingthe disease, and minimize user error which can cause unnecessarilydangerous situations in some circumstances.

SUMMARY OF THE INVENTION

Systems and methods for monitoring glucose are provided that offer oneor more benefits and/or advantages, for example, easing the burdensfaced by diabetic patients, simplifying the processes involved intreating diabetes, and minimizing user error which can causeunnecessarily dangerous situations in some circumstances.

Accordingly, in a first aspect, an integrated system for monitoring andtreating diabetes is provided, the system comprising: a medicamentinjection pen configured and arranged for injecting an amount of amedicament into a host; and an integrated receiver configured andarranged to receive sensor data from a continuous glucose sensor,wherein the sensor data is indicative of a glucose concentration of thehost in vivo, wherein the integrated receiver comprises electronicsconfigured and arranged to process the sensor data.

In an embodiment of the first aspect, the electronics are furtherconfigured to calculate at least one of time of medicament therapy andamount of medicament therapy.

In an embodiment of the first aspect, the integrated receiver comprisesa housing, wherein the medicament injection pen is integrally formedwith the housing.

In an embodiment of the first aspect, the integrated receiver comprisesa housing, and wherein the medicament injection pen is detachablyconnectable to the housing.

In an embodiment of the first aspect, communication between themedicament injection pen and the receiver is initiated based at least inpart on detachable connection of the medicament injection pen and thehousing.

In an embodiment of the first aspect, the integrated system furthercomprises a user interface configured and arranged for at least one ofinput of host information, output of sensor data, and medicamenttherapy.

In an embodiment of the first aspect, the user interface is furtherconfigured to display a graphical representation of at least one ofsensor data and medicament delivery data, wherein a solid linerepresents at least one of a target glucose concentration and a range.

In an embodiment of the first aspect, the integrated electronics areconfigured and arranged to require validation prior to injecting anamount of medicament into the host.

In an embodiment of the first aspect, the receiver is configured tocommunicate in at least one of wiredly with a single-point glucosemonitor and wirelessly with a single-point glucose monitor.

In an embodiment of the first aspect, the medicament injection pencomprises a motor.

In an embodiment of the first aspect, the motor is configured to set theamount of medicament.

In an embodiment of the first aspect, the motor is configured to controla rate of medicament injection into a host.

In an embodiment of the first aspect, the receiver is configured toremotely control the motor.

In an embodiment of the first aspect, the medicament injection pen andthe receiver each comprise mutually engaging electrical contacts, andwherein the mutually engaging electrical contacts are configured toallow communication between the medicament injection pen and thereceiver.

In an embodiment of the first aspect, the system is configured toinitiate communication between the medicament injection pen and thereceiver in response to engagement of the electrical contacts.

In an embodiment of the first aspect, the system is configured tocommunicate medicament delivery data between the medicament injectionpen and the receiver in response to engagement of the electricalcontacts.

In an embodiment of the first aspect, the integrated system furthercomprises a receptacle configured and arranged to receive at least oneof parts associated with the medicament injection pen and accessoriesassociated with the medicament injection pen.

In an embodiment of the first aspect, at least one of the partsassociated with the medicament injection pen and accessories associatedwith the medicament injection pen comprise a medicament cartridge.

In an embodiment of the first aspect, the integrated system furthercomprises a medicament injection pen kit, wherein the medicamentinjection pen kit is configured to receive the medicament injection pen,and wherein the medicament injection pen kit comprises a housingcomprising a user interface, and wherein the integrated receiver islocated within the housing and operably connected to the user interface.

In a second aspect an integrated system for monitoring and treatingdiabetes is provided, the system comprising: a receiver configured andarranged to receive sensor data from an operably connected continuousglucose sensor, wherein the continuous glucose sensor is configured andarranged to generate sensor data associated with a glucose concentrationof a host; integrated electronics configured to process the sensor dataand to generate a medicament therapy; and a medicament injection penconfigured to inject an amount of medicament into the host.

In an embodiment of the second aspect, the medicament therapy comprisesat least one of an amount of medicament therapy and a time of medicamenttherapy delivery.

In an embodiment of the second aspect, the receiver and the medicamentinjection pen are integrally formed.

In an embodiment of the second aspect, the integrated system furthercomprises a receptacle configured and arranged to receive at least oneof parts associated with the medicament injection pen and accessoriesassociated with the medicament injection pen.

In an embodiment of the second aspect, the medicament injection pen isdetachably connectable to the receiver.

In an embodiment of the second aspect, the medicament injection pen andreceiver each comprise mutually engaging electrical contacts, andwherein the mutually engaging electrical contacts are configured toallow communication between the medicament injection pen and thereceiver.

In an embodiment of the second aspect, the system is configured toinitiate communication between the medicament injection pen and thereceiver in response to engagement of the mutually engaging electricalcontacts.

In an embodiment of the second aspect, the system is configured tocommunicate the medicament therapy between the receiver and themedicament injection pen in response to engagement of the mutuallyengaging electrical contacts.

In an embodiment of the second aspect, the integrated system furthercomprises a housing integrally formed with the receiver, wherein theintegrated electronics are located with the housing.

In an embodiment of the second aspect, the medicament injection pen isdetachably connectable with the housing.

In an embodiment of the second aspect, the receiver further comprises auser interface, wherein the integrated electronics are configured todisplay at least one of sensor data and the medicament therapy thereon.

In an embodiment of the second aspect, the receiver comprises a housing,and wherein the user interface is located on the receiver housing.

In an embodiment of the second aspect, the integrated system furthercomprises a user interface configured to display at least one of thesensor data and the medicament therapy.

In an embodiment of the second aspect, the integrated electronics arefurther configured to display a representation of medicament delivery onthe user interface, and wherein the representation of medicamentdelivery is substantially adjacent to substantially time-correspondingsensor data.

In an embodiment of the second aspect, the integrated electronics arefurther configured to display a representation of sensor data on theuser interface, wherein the representation comprises at least one of atarget glucose concentration and a range.

In an embodiment of the second aspect, the user interface comprises aflexible LED screen operably connected to at least one of the receiverand the medicament injection pen, and wherein the integrated electronicsare configured to display continuous glucose sensor data on the flexibleLED screen.

In an embodiment of the second aspect, the user interface comprises animage projection system configured to project continuous glucose sensordata onto a surface.

In an embodiment of the second aspect, the medicament injection pencomprises a motor.

In an embodiment of the second aspect, the motor is configured toautomatically set the amount of medicament.

In an embodiment of the second aspect, the motor is configured tocontrol a rate of medicament injection into the host.

In an embodiment of the second aspect, the receiver is configured toremotely control the motor.

In an embodiment of the second aspect, the integrated system furthercomprises a medicament injection pen kit comprising the receiver and theintegrated electronics, wherein the medicament injection pen kit isconfigured to receive the medicament injection pen.

In an embodiment of the second aspect, the integrated system furthercomprises a user interface, wherein the integrated electronics areconfigured to display at least one of sensor data and the medicamenttherapy thereon.

In an embodiment of the second aspect, the medicament injection pen kitfurther comprises a receptacle configured and arranged to receive atleast one of a medicament cartridge and a medicament injection penneedle.

In a third aspect, a method for monitoring and treating diabetes usingan integrated diabetes monitoring and treatment device is provided, themethod comprising: receiving sensor data from a continuous glucosesensor, wherein the sensor data is associated with a glucoseconcentration of a host; processing the sensor data; generating amedicament therapy; and injecting an amount of medicament into the hostbased at least in part on the generated medicament therapy.

In an embodiment of the third aspect, the step of generating amedicament therapy comprises determining at least one of an amount ofmedicament to be delivered and a time of medicament delivery.

In an embodiment of the third aspect, the step of injecting comprisessetting the amount of medicament.

In an embodiment of the third aspect, the step of setting the amount ofmedicament comprises setting a medicament injection rate.

In an embodiment of the third aspect, the step of setting the amount ofmedicament comprises remotely setting the amount of medicament.

In a fourth aspect, an integrated system for monitoring and treatingdiabetes is provided, the system comprising: a sensor, the sensorcomprising a continuous glucose sensor configured to continuously detecta signal associated with a glucose concentration of a host, a processormodule configured and arranged to process the signal to generate atherapy, and a communication module configured and arranged tocommunicate the therapy instruction to a medicament delivery device; andat least one medicament delivery device configured and arranged todeliver a medicament therapy to the host based at least in part on thecommunicated therapy instruction.

In an embodiment of the fourth aspect, the medicament therapy comprisesat least one of a medicament type, a medicament amount, and a deliverytime.

In an embodiment of the fourth aspect, the sensor further comprises aninput module configured to receive host information, and wherein theprocessor module is further configured to process the host information.

In an embodiment of the fourth aspect, the input module is configured toreceive information from at least one of a user interface, a medicamentdelivery device, an infusion pump, a patient monitor, and a single-pointglucose monitor.

In an embodiment of the fourth aspect, the integrated system furthercomprises a display module configured and arranged to display of hostinformation, sensor data, the therapy instruction, an alert and/or analarm.

In an embodiment of the fourth aspect, the communication module isconfigured to communication wirelessly with the medicament deliverydevice.

In an embodiment of the fourth aspect, the communication module isfurther configured to communicate the therapy instruction responsive tointerrogation by the medicament delivery device.

In an embodiment of the fourth aspect, the medicament delivery device isconfigured for communication with a plurality of sensors.

In an embodiment of the fourth aspect, the medicament delivery device isconfigured for medicament delivery to a plurality of different hosts,based at least in part on a therapy instruction from a sensor.

In an embodiment of the fourth aspect, the medicament delivery device isa hand-held injector pen.

In an embodiment of the fourth aspect, the medicament delivery device isconfigured and arranged for aseptic medicament delivery to a pluralityof hosts.

In an embodiment of the fourth aspect, at least one of the sensor anddelivery device is configured transmit data to a data repository.

In a fifth aspect, a method for monitoring and treating diabetes usingan integrated diabetes monitoring and treatment system is provided, themethod comprising: continuously detecting a signal associated with aglucose concentration of a host; processing the signal; generating atherapy instruction; communicating the therapy instruction to at leastone medicament delivery device; and delivering a medicament therapy tothe host based at least in part on the communicated therapy instruction.

In an embodiment of the fifth aspect, the method further comprisesreceiving and processing host information.

In an embodiment of the fifth aspect, the method further comprisesremotely programming the system.

In an embodiment of the fifth aspect, the step of generating the therapyinstruction comprises determining at least one of a type of medicament,a medicament amount, and a delivery time.

In an embodiment of the fifth aspect, the method further comprisesreceiving information from at least one of a user interface, amedicament delivery device, an infusion pump, a patient monitor, and asingle-point glucose monitor.

In an embodiment of the fifth aspect, the method further comprisesdisplaying at least one of host information, sensor data, the therapyinstruction, an alert, and an alarm.

In an embodiment of the fifth aspect, the step of communicating furthercomprises communicating wirelessly.

In an embodiment of the fifth aspect, the step of communicating furthercomprises communicating the therapy instruction based at least in parton interrogation by the medicament delivery device.

In an embodiment of the fifth aspect, the step of communicating furthercomprises communicating to a medicament delivery device configured formedicament delivery to a plurality of hosts, based at least in part on atherapy instruction communicated by an integrated system worn by eachhost.

In an embodiment of the fifth aspect, the step of communicating furthercomprises communicating to a hand-held injector pen.

In an embodiment of the fifth aspect, the step of communicating furthercomprises communicating to a medicament delivery device configured andarranged for aseptic medicament delivery to a plurality of hosts.

In an embodiment of the fifth aspect, the step of communicating furthercomprises transmitting data to a data repository.

In a sixth aspect, a medicament delivery device for monitoring andtreating at least one of a plurality of hosts is provided, themedicament delivery device comprising: a communication module configuredto interrogate a continuous glucose sensor and to receive sensor datatherefrom, wherein the sensor data comprises a signal associated with ananalyte concentration of a host; a processor module configured toprocess the sensor data and calculate a medicament therapy, wherein theprocessor module comprises programming for calculating the medicamenttherapy based at least in part on the sensor data; and a hand-heldinjector pen configured and arranged to deliver a medicament to thehost, based at least in part on the medicament therapy.

In an embodiment of the sixth aspect, the medicament delivery devicefurther comprises a user interface configured and arranged for at leastone of input of at least some medical information and display of atleast some medical information, wherein medical information comprises atleast one of host information, received sensor data, processed sensordata, the calculated medicament therapy, a delivered medicament therapy,an instruction, an alert, an alarm, and a failsafe.

In an embodiment of the sixth aspect, the user interface is detachablyconnected to the hand-held injector pen.

In an embodiment of the sixth aspect, host information comprises atleast one of a host information, type of medicament to be delivered, aglucose target, predicted hypoglycemia, predicted hypoglycemia, atherapy protocol, an alert, and an alarm.

In an embodiment of the sixth aspect, the processor module is furtherconfigured for validation of the medicament therapy.

In an embodiment of the sixth aspect, the medicament therapy comprisesat least one of a type of medicament to be delivered, an amount ofmedicament to be delivered and a time of delivery.

In an embodiment of the sixth aspect, the communication module isfurther configured to communicate treatment information to a centralmonitor, wherein the treatment information comprises at least one ofhost information, sensor data, the medicament therapy, and deliveredmedicament information.

In an embodiment of the sixth aspect, the communication module isconfigured for wireless communication.

In an embodiment of the sixth aspect, the wireless communication isselected from the group consisting of RF communication, IRcommunication, Bluetooth communication, and inductive coupling.

In an embodiment of the sixth aspect, the communication module and themedicament delivery device are integrally formed.

In an embodiment of the sixth aspect, the communication module and themedicament delivery device are detachably connected.

In an embodiment of the sixth aspect, the injector pen is configured foraseptic medicament delivery to a plurality of hosts.

In an embodiment of the sixth aspect, the injector pen is configured andarranged for pneumatic aseptic medicament delivery.

In an embodiment of the sixth aspect, the injector pen comprises acartridge comprising a plurality of single-use needles.

In an embodiment of the sixth aspect, the cartridge is configured andarranged for automatic installation of a clean needle after a medicamentdelivery.

In a seventh aspect, a method for monitoring and treating diabetes inone of a plurality of hosts is provided, the method comprising:interrogating a continuous glucose sensor; receiving sensor data fromthe continuous glucose sensor, wherein the sensor data comprises asignal associated with an analyte concentration of a first host;processing the sensor data; calculating a medicament therapy based atleast in part on the sensor data; and delivering an amount of amedicament to the first host, based at least in part on the calculatedmedicament therapy.

In an embodiment of the seventh aspect, the steps of interrogating,receiving, processing, calculating and delivering are repeated with asecond host.

In an embodiment of the seventh aspect, the method further comprises astep of at least one of inputting at least some medical information anddisplaying at least some medical information, wherein medicalinformation comprises at least one of host information, received sensordata, processed sensor data, the calculated medicament therapy, adelivered medicament therapy, an instruction, an alert, an alarm, and afailsafe.

In an embodiment of the seventh aspect, the method further comprisesdetachably connecting a user interface.

In an embodiment of the seventh aspect, the method further comprisesvalidating the medicament therapy.

In an embodiment of the seventh aspect, the method further comprisescommunicating treatment information to a central monitor, wherein thetreatment information comprises at least one of host information, sensordata, the medicament therapy, and delivered medicament information.

In an embodiment of the seventh aspect, the step of communicatingcomprises communicating wirelessly.

In an embodiment of the seventh aspect, the steps of interrogating andreceiving comprise communicating wirelessly.

In an embodiment of the seventh aspect, the step of delivering comprisesaseptically delivering the medicament to a plurality of hosts.

In an embodiment of the seventh aspect, the step of delivering comprisespneumatically aseptically delivering the medicament.

In an embodiment of the seventh aspect, the step of delivering comprisesautomatically installing a clean needle after medicament delivery.

In an eighth aspect, an integrated system for monitoring and treatingdiabetes is provided, the system comprising: a receiver configured andarranged to receive continuous glucose sensor data from a continuousglucose sensor; a processor module configured to process the continuousglucose sensor data and to provide first and second medicament dosinginformation based at least in part on the continuous glucose sensordata; and a communication module configured and arranged to communicatethe medicament dosing information with a first integrated medicamentdelivery device and a second integrated medicament delivery device.

In an embodiment of the eighth aspect, the first medicament dosinginformation comprises a basal medicament dose and the first integratedmedicament delivery device comprises a basal medicament delivery device.

In an embodiment of the eighth aspect, the basal medicament deliverydevice comprises a medicament pump configured to infuse a firstmedicament.

In an embodiment of the eighth aspect, the processor module comprisesprogramming to calculate a basal dose based at least in part on thecontinuous glucose sensor data.

In an embodiment of the eighth aspect, the second medicament dosinginformation comprises a bolus medicament dose and the second integratedmedicament delivery device comprises a bolus medicament delivery device.

In an embodiment of the eighth aspect, the processor module comprisesprogramming to calculate a bolus dose based at least in part on thecontinuous glucose sensor data.

In an embodiment of the eighth aspect, the bolus medicament deliverydevice comprises a hand-held medicament injection pen configured toinfuse a second medicament.

In an embodiment of the eighth aspect, the bolus medicament deliverydevice comprises a motor configured to automatically set the amount ofmedicament and the medicament dosing information comprises aninstruction for the medicament delivery device to automatically portionout the bolus dose, whereby the portioned out bolus dose can be manuallydelivered by the host.

In an embodiment of the eighth aspect, the bolus medicament deliverydevice comprises a motor to control a rate of medicament injection intothe host.

In an embodiment of the eighth aspect, the integrated system furthercomprises a user interface configured and arranged to display at leastone of continuous glucose sensor data and medicament dosing information.

In an embodiment of the eighth aspect, the user interface is furtherconfigured for input of at least one of host information and medicamentdelivery device information.

In an embodiment of the eighth aspect, the host information comprises atleast one of host identity, host physical state, target glucoseconcentration and type of medicament to be delivered.

In an embodiment of the eighth aspect, the medicament deliveryinformation comprises at least one of host identity, identification of afunctionally connected medicament delivery device, a type of medicamentto be delivered, a medicament delivery profile, a medicament deliveryprotocol, and a failsafe.

In an embodiment of the eighth aspect, the communication modulecomprises a communication module configured and arranged to interrogateand/or provide medicament dosing information to the first medicamentdelivery device and the second medicament delivery device.

In an embodiment of the eighth aspect, the receiver comprises thecommunication module and the processor module, and wherein the receiverwirelessly communicates with the first and second medicament deliverydevices.

In an embodiment of the eighth aspect, the receiver comprises thecommunication module and the processor module, and wherein the receiveris physically connected to at least one of the first medicament deliverydevice and the second medicament delivery device.

In a ninth aspect, a method of self-monitoring and self-treatingdiabetes is provided, the method comprising: receiving continuousglucose sensor data from an operably connected continuous glucosesensor; processing the continuous glucose sensor data; calculatingmedicament dosing information for at least two integrated medicamentdelivery devices based at least in part on the continuous glucose sensordata; and communicating the medicament dosing information with theintegrated medicament delivery devices.

In an embodiment of the ninth aspect, the step of calculating medicamentdosing information comprises calculating a basal dose based at least inpart on the continuous glucose sensor data.

In an embodiment of the ninth aspect, the step of communicatingcomprises communicating the basal medicament dose to a medicament pump.

In an embodiment of the ninth aspect, the method further comprisesinfusing the basal medicament dose.

In an embodiment of the ninth aspect, the step of providing medicamentdosing information comprises calculating a bolus dose based at least inpart on the continuous glucose sensor data.

In an embodiment of the ninth aspect, the step of communicatingcomprises communicating the bolus medicament dose to a hand-heldinjector pen.

In an embodiment of the ninth aspect, the step of delivering comprisesinjecting the bolus medicament dose.

In an embodiment of the ninth aspect, the step of communicating thebolus dose further comprises providing an instruction to automaticallyset at least one of the amount of medicament and rate of delivery basedat least in part on the medicament dosing information.

In an embodiment of the ninth aspect, the step of delivering the bolusdose further comprises automatically setting the amount of medicamentbased at least in part on the provided instruction.

In an embodiment of the ninth aspect, the step of delivering the bolusdose further comprises automatically setting the rate of delivery basedat least in part on the provided instruction.

In an embodiment of the ninth aspect, the method further comprisesdisplaying at least one of continuous glucose sensor data and medicamentdosing information.

In an embodiment of the ninth aspect, the method further comprisesinputting at least one of host information and medicament deliverydevice information.

In an embodiment of the ninth aspect, the step of communicatingcomprises wirelessly communicating.

In an embodiment of the ninth aspect, the step of wirelesslycommunicating comprises interrogating and/or providing medicament dosinginformation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an integrated system of the preferredembodiments, including a continuous glucose sensor, a receiver forprocessing and displaying sensor data, a hand-held medicament injectionpen, and an optional single point glucose-monitoring device.

FIG. 2A is a perspective view of a wholly implantable continuous glucosesensor, in one embodiment.

FIG. 2B is a perspective view of an in vivo portion of a continuousglucose sensor, in one embodiment.

FIG. 2C is a cross-section of the continuous glucose sensor of FIG. 2B,taken on line 2C-2C, in one embodiment.

FIG. 2D is a perspective view of an in vivo portion of a continuousglucose sensor including two working electrodes, in one embodiment.

FIG. 2E illustrates a continuous glucose sensor implanted in avein/artery, in one embodiment.

FIG. 3 is a perspective view of an integrated system in one embodiment,showing an LCD screen on a hand-held medicament injection pen housing.

FIG. 4 is a perspective view of an integrated system in anotherembodiment, showing an LCD screen on a hand-held medicament injectionpen housing.

FIG. 5 is a perspective view of an integrated system in anotherembodiment, showing a housing configured to receive a hand-heldmedicament injection pen, wherein the housing includes an LCD screenthereon.

FIG. 6 is a perspective view of an integrated system in anotherembodiment, showing a housing configured to receive a hand-heldmedicament injection pen, wherein the housing includes an LCD screenthereon.

FIG. 7 is a perspective view of an integrated system in anotherembodiment, showing a housing configured to receive a hand-heldmedicament injection pen, a receiver, integrated electronics, and a userinterface.

FIG. 8 is a perspective view of an integrated system in anotherembodiment, showing a hand-held medicament injection pen, a receiver,integrated electronics, and a user interface integrally formed and/orincorporated therein.

FIG. 9 is a perspective view of an integrated system in anotherembodiment, showing a receiver housing including a receiver, integratedelectronics, a user interface, and a hand-held medicament injection penintegrally formed therewith and/or incorporated therein.

FIG. 10 is a perspective view of an integrated system in anotherembodiment, showing a receiver housing including a receiver, integratedelectronics, a user interface, and a hand-held medicament injection penintegrally formed therewith and/or incorporated therein.

FIG. 11 is a perspective view of an integrated system showing anintegrated housing including a receiver, integrated electronics, a userinterface, and a hand-held medicament injection pen, wherein the housingfurther includes a cap for the hand-held medicament injection pen.

FIG. 12 is a perspective view of an integrated system showing anintegrated housing including a receiver, integrated electronics, a userinterface, and a hand-held medicament injection pen, wherein the housingfurther includes a cap.

FIG. 13 is a block diagram that illustrates integrated electronics inone embodiment.

FIG. 14 is graphical representation of integrated data that can bedisplayed on an LCD screen, for example, in one embodiment.

FIG. 15 is a flow chart that illustrates the process of validatingtherapy instructions prior to medicament delivery in one embodiment.

FIG. 16 is a flow chart that illustrates the process of providingadaptive metabolic control using an integrated sensor and hand-heldmedicament injection pen in one embodiment.

FIG. 17 is a block diagram illustrating an integrated system, in oneembodiment, including a continuous glucose sensor and a plurality ofhand-held medicament injection pens, in one embodiment.

FIG. 18 is a block diagram illustrating an integrated system, in oneembodiment, including a plurality of continuous glucose sensors and ahand-held medicament injection pen, in one embodiment.

FIG. 19 is a block diagram illustrating an integrated system, in oneembodiment, including a continuous glucose sensor, a receiver, a basalmedicament delivery device and a bolus medicament delivery device, inone embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The following description and examples illustrate some exemplaryembodiments of the disclosed invention in detail. Those of skill in theart will recognize that there are numerous variations and modificationsof this invention that are encompassed by its scope. Accordingly, thedescription of a certain exemplary embodiment should not be deemed tolimit the scope of the present invention.

Definitions

In order to facilitate an understanding of the preferred embodiments, anumber of terms are defined below.

The term “algorithm” as used herein is a broad term, and is to be givenits ordinary and customary meaning to a person of ordinary skill in theart (and is not to be limited to a special or customized meaning), andrefers without limitation to a computational process (for example,programs) involved in transforming information from one state toanother, for example, by using computer processing.

The term “basal,” as used herein is a broad term, and is to be given itsordinary and customary meaning to a person of ordinary skill in the art(and is not to be limited to a special or customized meaning), andrefers without limitation to the minimum required rate or other valuefor something to function. For example, in the case of medicamenttherapy, the term “basal rate” can refer to a regular (e.g., inaccordance with fixed order or procedure, such as regularly scheduledfor/at a fixed time), periodic or continuous delivery of low levels ofmedicament, such as but not limited to throughout a 24-hour period.

The term “basal profile,” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a person of ordinary skillin the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to a medicament deliveryschedule that includes one or more blocks of time (e.g., time blocks),wherein each block is associated with a maximum medicament deliveryrate.

The term “biological sample” as used herein is a broad term, and is tobe given its ordinary and customary meaning to a person of ordinaryskill in the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to sample of a host body, forexample blood, interstitial fluid, spinal fluid, saliva, urine, tears,sweat, or the like.

The term “bolus,” as used herein is a broad term, and is to be given itsordinary and customary meaning to a person of ordinary skill in the art(and is not to be limited to a special or customized meaning), andrefers without limitation to a single dose of medicament, usually givenover a short, defined period of time. In one exemplary embodiment, abolus of medicament is calculated and/or estimated to be sufficient tocover an expected rise in blood glucose, such as the rise that generallyoccurs during/after a meal.

The term “continuous (or continual) analyte sensing” as used herein is abroad term, and is to be given its ordinary and customary meaning to aperson of ordinary skill in the art (and is not to be limited to aspecial or customized meaning), and refers without limitation to theperiod in which monitoring of analyte concentration is continuously,continually, and or intermittently (regularly or irregularly) performed,for example, about every 5 to 10 minutes.

The phrase “continuous glucose sensing” as used herein is a broad term,and is to be given its ordinary and customary meaning to a person ofordinary skill in the art (and is not to be limited to a special orcustomized meaning), and refers without limitation to the period inwhich monitoring of plasma glucose concentration is continuously orcontinually performed, for example, at time intervals ranging fromfractions of a second up to, for example, 1, 2, or 5 minutes, or longer.

The term “count” as used herein is a broad term, and is to be given itsordinary and customary meaning to a person of ordinary skill in the art(and is not to be limited to a special or customized meaning), andrefers without limitation to a unit of measurement of a digital signal.For example, a raw data stream or raw data signal measured in counts isdirectly related to a voltage (for example, converted by an A/Dconverter), which is directly related to current from the workingelectrode.

The term “electrochemically reactive surface” as used herein is a broadterm, and is to be given its ordinary and customary meaning to a personof ordinary skill in the art (and is not to be limited to a special orcustomized meaning), and refers without limitation to the surface of anelectrode where an electrochemical reaction takes place. For example, aworking electrode measures hydrogen peroxide produced by theenzyme-catalyzed reaction of the analyte detected, which reacts tocreate an electric current. Glucose analyte can be detected utilizingglucose oxidase, which produces H₂O₂ as a byproduct. H₂O₂ reacts withthe surface of the working electrode, producing two protons (2H+), twoelectrons (2e⁻) and one molecule of oxygen (O₂), which produces theelectronic current being detected.

The term “electronic connection” as used herein is a broad term, and isto be given its ordinary and customary meaning to a person of ordinaryskill in the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to any electronic connectionknown to those in the art. In one exemplary embodiment, a connection isbetween the sensing region electrodes and the electronic circuitry of adevice that provides electrical communication, such as mechanical (forexample, pin and socket) or soldered electronic connections.

The term “host” as used herein is a broad term, and is to be given itsordinary and customary meaning to a person of ordinary skill in the art(and is not to be limited to a special or customized meaning), andrefers without limitation to mammals, particularly humans.

The term “host information” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a person of ordinary skillin the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to information related to thehost, such as a patient using an integrated system of the preferredembodiments, such as but not limited to a continuous glucose sensor, amedicament delivery device, and/or receiving medicament therapy. In someembodiments, the medicament is insulin or another injectable diabetesmedicament, such as but not limited to pramlintide, exenatide, amylin,glucagon, and the like. In some embodiments, host information includesbut is not limited to information relating to the host and his/hertherapy, such as but not limited to information used to identify thehost (e.g., in a clinical setting), such as a host identification numberand/or code, host physical characteristics, host health information(e.g., medical conditions, diseases, illnesses), host exerciseinformation, a therapy protocol, such as but not limited to a medicamenttherapy protocol assigned to the host, including but not limited to oneor more types of medicament the host is to receive and/or target glucoseconcentration(s), an alarm, an alert and/or an instruction.

The term “integrated,” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a person of ordinary skillin the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to united, bringing togetherprocesses or functions.

The term “interrogate,” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a person of ordinary skillin the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to give or send out a signal to(e.g., as a transponder) for triggering an appropriate response toobtain data or information from (a device, database, etc.).

The term “medicament therapy,” as used herein is a broad term, and is tobe given its ordinary and customary meaning to a person of ordinaryskill in the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to an identity, an amount and/orschedule of a medicament to be delivered to the host. In someembodiments, the medicament is a diabetes-treating medicament formulatedfor injection, such as but not limited to insulin, pramlintide,exenatide, amylin, glucagon, derivatives thereof, and the like. In otherembodiments, the medicament is one for treating another disease and isformulated for injection.

The terms “operatively connected,” “operatively linked,” “operablyconnected,” and “operably linked” as used herein are broad terms, andare to be given their ordinary and customary meaning to a person ofordinary skill in the art (and are not to be limited to a special orcustomized meaning), and refer without limitation to one or morecomponents linked to one or more other components. The terms can referto a mechanical connection, an electrical connection, or a connectionthat allows transmission of signals between the components (e.g.,including a wireless connection). For example, one or more electrodescan be used to detect the amount of analyte in a sample and to convertthat information into a signal; the signal can then be transmitted to acircuit. In such an example, the electrode is “operably linked” to theelectronic circuitry.

The terms “processor module” and “processor” as used herein are broadterms, and are to be given their ordinary and customary meaning to aperson of ordinary skill in the art (and are not to be limited to aspecial or customized meaning), and refer without limitation to acomputer system, state machine, processor, or the like designed toperform arithmetic or logic operations using logic circuitry thatresponds to and processes the basic instructions that drive a computer.In some embodiments, the term processor includes storage, e.g., ROM andRAM.

The term “range,” as used herein is a broad term, and is to be given itsordinary and customary meaning to a person of ordinary skill in the art(and is not to be limited to a special or customized meaning), andrefers without limitation to a sequence, series, or scale between limits(e.g., maximum and minimum values). For example, a range of glucoseconcentrations can include glucose concentrations from 60 mg/dl to 200mg/dl. In another example, a range of medicament delivery rates caninclude rates from about 0.01 U/hr to about 40 U/hr. In someembodiments, a range is a single value.

The terms “sensor,” “sensing region” as used herein are broad terms, andare to be given their ordinary and customary meaning to a person ofordinary skill in the art (and are not to be limited to a special orcustomized meaning), and refer without limitation to the component orregion of a device by which an analyte can be quantified.

The terms “smoothing” and “filtering” as used herein are broad terms,and are to be given their ordinary and customary meaning to a person ofordinary skill in the art (and are not to be limited to a special orcustomized meaning), and refer without limitation to modification of aset of data to make it smoother and more continuous or to remove ordiminish outlying points, for example, by performing a moving average.

The term “single point glucose monitor” as used herein is a broad term,and is to be given its ordinary and customary meaning to a person ofordinary skill in the art (and is not to be limited to a special orcustomized meaning), and refers without limitation to a device that canbe used to measure a glucose concentration within a host at a singlepoint in time, for example, a finger stick blood glucose meter. Itshould be understood that single point glucose monitors can measuremultiple samples (for example, blood or interstitial fluid); howeveronly one sample is measured at a time and typically requires some userinitiation and/or interaction.

The term “target range,” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a person of ordinary skillin the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to a range of glucoseconcentrations within which a host is to try to maintain his bloodsugar. In general, a target range is a range of glucose concentrationsconsidered to be euglycemic. Euglycemic glucose concentrations arediscussed in detail in the section entitled “Programming andProcessing.”

The term “therapy instruction,” as used herein is a broad term, and isto be given its ordinary and customary meaning to a person of ordinaryskill in the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to an instruction to amedicament delivery device, such as a medicament injection pen or andmedicament pump, to deliver a medicament therapy to a host, includingbut not limited to an amount of medicament to be delivered and/or a timeof medicament delivery.

The terms “substantial” and “substantially” as used herein are broadterms, and are to be given their ordinary and customary meaning to aperson of ordinary skill in the art (and are not to be limited to aspecial or customized meaning), and refer without limitation to asufficient amount that provides a desired function. In some embodiments,the term “substantially” includes an amount greater than 50 percent, anamount greater than 60 percent, an amount greater than 70 percent, anamount greater than 80 percent, and/or an amount greater than 90percent. In some embodiments, the integrated electronics are configuredto display a representation of medicament delivery on the user interfacesubstantially adjacent to substantially time-corresponding sensor data,wherein “substantially adjacent” refers to a location sufficiently nearby or close to the relevant data to create an association, for example.

Overview

FIG. 1 is a block diagram of an integrated system 10 of the preferredembodiments, including a continuous glucose sensor 12, a receiver 14 forprocessing and displaying sensor data, a medicament delivery device 16,and optionally a single point glucose-monitoring device 18. Theintegrated diabetes management system 10 of the preferred embodimentsprovides improved convenience and accuracy thus affording a host 8 withimproved convenience, functionality, and safety in the care of theirdisease.

FIG. 1 shows a continuous glucose sensor 12 that measures aconcentration of glucose or a substance indicative of the concentrationor presence of the glucose. In some embodiments, the glucose sensor 12is an invasive, minimally invasive, or non-invasive device, for examplea subcutaneous, transdermal, or intravascular device, as describedelsewhere herein. In some embodiments, the sensor 12 can analyze aplurality of intermittent biological samples. The glucose sensor can useany method of glucose-measurement, including enzymatic, chemical,physical, electrochemical, spectrophotometric, polarimetric,calorimetric, radiometric, or the like. In alternative embodiments, thesensor 12 can be any sensor capable of determining the level of ananalyte in the body, for example oxygen, lactase, insulin, hormones,cholesterol, medicaments, viruses, or the like. The glucose sensor 12uses any known method to provide an output signal indicative of theconcentration of the glucose. The output signal is typically a raw datastream that is used to provide a useful value of the measured glucoseconcentration to a patient or doctor, for example.

A receiver 14 is provided that receives and processes the raw datastream, including calibrating, validating, and displaying meaningfulglucose values to a host, such as described in more detail below.Although the receiver is shown as wirelessly communicating with thesensor, the receiver can be physically connected to the sensor and/orsensor electronics and/or housed within the medicament delivery deviceand/or single point monitor, thereby removing the wireless connection. Amedicament delivery device 16 is further provided as a part of theintegrated system 10. In some preferred embodiments, the medicamentdelivery device 16 is a medicament injection pen or jet-type injectorfor injecting a medicament (e.g., insulin). In some preferredembodiments, the medicament delivery device 16 is a medicament deliverypump, also referred to as an infusion pump, for medicament infusion(e.g., insulin). In some embodiments, both a hand-held medicamentinjection pen and an infusion pump are used to deliver one or more typesof medicament to the host, as described elsewhere herein in greaterdetail. In some embodiments, an optional single point glucose monitor 18is further provided as a part of the integrated system 10, for example aself-monitoring blood glucose meter (SMBG), non-invasive glucose meter,or the like, integrated into a receiver housing and/or a medicamentdelivery device housing.

Conventionally, each of these devices separately provides valuableinformation and/or services to diabetic patients. Thus, a typicaldiabetic patient has numerous individual devices, which they track andconsider separately. In some cases, the amount of information providedby these individual devices may require complex understanding of thenuances and implications of each device, for example types and amountsof medicament (e.g., insulin) to deliver. Typically, each individualdevice is a silo of information that functions as well as the dataprovided therein, therefore when the devices are able to communicatewith each other, enhanced functionality and safety can be realized. Forexample, when a continuous glucose monitor functions alone (for example,without data other than that which was gathered by the device), suddenchanges in glucose level are tracked, but may not be fully understood,predicted, preempted, or otherwise considered in the processing of thesensor data; however, when the continuous glucose sensor is providedwith information about time, amount, and type of medicament injections,calories consumed, time or day, meal time, or like, more meaningful,accurate and useful glucose estimation, prediction, and other suchprocessing can be provided, such as described in more detail herein. Byintegrating these devices, the information from each component can beleveraged to increase the intelligence, benefit provided, convenience,safety, and functionality of the continuous glucose sensor and the otherintegrated components. Therefore, it would be advantageous to provide adevice that aids the diabetic patient in integrating these individualdevices in the treatment of his/her disease.

Sensor

The preferred embodiments relate to the use of an analyte sensor 12 thatmeasures a concentration of analyte of interest or a substanceindicative of the concentration or presence of the analyte. In someembodiments, the sensor is a continuous device, for example asubcutaneous, transdermal (e.g., transcutaneous), or intravasculardevice. The analyte sensor can use any method of analyte-sensing,including enzymatic, chemical, physical, electrochemical,spectrophotometric, polarimetric, calorimetric, radiometric, or thelike.

The analyte sensor uses any method, including invasive, minimallyinvasive, and non-invasive sensing techniques, to provide an outputsignal indicative of the concentration of the analyte of interest. Theoutput signal, which is associated with the analyte concentration of thehost, is typically a raw signal that is used to provide a useful valueof the analyte of interest to a user, such as a patient or physician,who can be using the device. Accordingly, appropriate smoothing,calibration, and/or evaluation methods can be applied to the signaland/or system as a whole to provide relevant and acceptable estimatedanalyte data to the user.

FIG. 2A illustrates the continuous glucose sensor 12, in one embodiment,an implantable glucose sensor such as described in U.S. PatentPublication No. 2005-0245799, which is incorporated by reference in itsentirety. In this embodiment, a body 13 and a sensing region include theelectrodes and a membrane 12 c. Sensor electronics (not shown) arelocated within the body 13. The three electrodes, including but notlimited to a working electrode 12 a, a reference electrode 12 b, and anauxiliary, counter or second working electrode 12 x, within the sensingregion are operably connected to the sensor electronics and are coveredby a sensing membrane 12 c and an optionally biointerface membrane (notshown), which are described elsewhere herein. The body 13 is preferablyformed from epoxy molded around the sensor electronics, however the bodycan be formed from a variety of materials, including metals, ceramics,plastics, or composites thereof. U.S. Pat. No. 7,134,999, which isincorporated by reference in its entirety, discloses suitableconfigurations suitable for the body 13. In one embodiment, the sensingregion 12 c comprises three electrodes including a platinum workingelectrode 12 a, a platinum counter electrode 12 x, and a silver/silverchloride reference electrode 12 b, for example. However a variety ofelectrode materials and configurations can be used with the implantableglucose sensor of the preferred embodiments. The top ends of theelectrodes are in contact with an electrolyte phase (not shown), whichis a free-flowing fluid phase disposed between the sensing membrane andthe electrodes. In one embodiment, a counter electrode 12 x is providedto balance the current generated by the species being measured at theworking electrode. In the case of a glucose oxidase based glucosesensor, the species being measured at the working electrode is H₂O₂.Glucose oxidase catalyzes the conversion of oxygen and glucose tohydrogen peroxide and gluconate according to the following reaction:Glucose+O₂→Gluconate+H₂O₂

The change in H₂O₂ can be monitored to determine glucose concentrationbecause for each glucose molecule metabolized, there is a proportionalchange in the product H₂O₂. Oxidation of H₂O₂ by the working electrodeis balanced by reduction of ambient oxygen, enzyme generated H₂O₂, orother reducible species at the counter electrode. The H₂O₂ produced fromthe glucose oxidase reaction further reacts at the surface of workingelectrode and produces two protons (2H+), two electrons (2e⁻), and oneoxygen molecule (O₂). In an alternative embodiment, the continuousglucose sensor comprises a continuous glucose sensor such as describedwith reference to U.S. Pat. No. 6,579,690 to Bonnecaze et al. or U.S.Pat. No. 6,484,046 to Say et al. In another alternative embodiment, thecontinuous glucose sensor comprises a refillable subcutaneous sensorsuch as described with reference to U.S. Pat. No. 6,512,939 to Colvin etal. All of the above patents and/or patent applications are incorporatedin their entirety herein by reference.

FIG. 2B illustrates the continuous glucose sensor in another embodiment;the glucose sensor is described in more detail in U.S. PatentPublication No. US-2006-0020187-A1, U.S. Patent Publication No.US-2006-0142651-A1, U.S. Patent Publication No. US-2006-0270923-A1, U.S.Patent Publication No. US-2007-0027370-A1, U.S. Patent Publication No.US-2005-0143635-A1, U.S. Patent Publication No. US-2007-0027385-A1, U.S.Patent Publication No. US-2007-0213611-A1, and U.S. Patent PublicationNo. US-2008-0083617-A1, which are each incorporated herein by referencein their entirety. FIG. 2B is a perspective view of an in vivo portionof the continuous glucose sensor 12, in one embodiment. In thisembodiment, the in vivo portion of the sensor includes at least oneworking electrode 12 a and a reference electrode 12 b and a sensingmembrane 12 c (dashed line). In one alternative embodiment, thecontinuous glucose sensor comprises a glucose sensor such as describedin U.S. Pat. No. 6,565,509 to Say et al., U.S. Pat. No. 6,360,888 toMcIvor et al. and/or U.S. Pat. No. 6,424,847 to Mastrototaro et al. Allof the above patents and/or patent applications are incorporated intheir entirety herein by reference.

FIG. 2C is a cross-section of the sensor shown in FIG. 2B, taken on line2C-2C. In preferred embodiments, the membrane 12 c (e.g., a biointerfaceand/or sensing membrane) includes at least an enzyme domain 12 f havingan enzyme configured to detect the analyte, such as but not limited toglucose oxidase (e.g., GOX). In some preferred embodiments, the sensingmembrane 12 c can include one or more additional domains, such as butnot limited to an electrode domain 12 d, an interference domain 12 e, aresistance domain 12 j, a cell disruptive domain and/or a cellimpermeable domain, for example. Additional sensor and membraneconfigurations can be found in U.S. Patent Publication No.US-2006-0020187-A1, U.S. Patent Publication No. US-2005-0031689-A1, U.S.Patent Publication No. US-2007-0027370-A1, U.S. Patent Publication No.US-2006-0229512-A1, U.S. Patent Publication No. US-2006-0253012-A1, U.S.Patent Publication No. US-2007-0197890-A1, U.S. Patent Publication No.US-2007-0244379, and U.S. Patent Publication No. US-2007-0235331-A1,each of which is incorporated herein by reference in its entirety.

FIG. 2D illustrates the continuous glucose sensor in another embodiment,a glucose sensor having first and second working electrodes (e.g.,dual-electrode), such as described in U.S. Patent Publication No.US-2007-0027385-A1, U.S. Patent Publication No. US-2007-0213611-A1, andU.S. Patent Publication No. US-2008-0083617-A1, U.S. Pat. No. 7,366,556,and co-pending U.S. patent application Ser. No. 12/111,062, filed Apr.28, 2008 and entitled “Dual Electrode System for a Continuous AnalyteSensor,” each of which are incorporated herein by reference in theirentireties. In some preferred embodiments, the dual-electrode continuousglucose sensor includes a first working electrode 12 a ₁ and a secondworking electrode 12 a ₂, and a reference electrode 12 b, and a membranesystem (not shown), wherein the membrane located over the first workingelectrode comprises active enzyme and the located over the secondworking electrode comprises no enzyme or inactive enzyme. Accordingly, atotal signal detected by the first working electrode comprisesanalyte-related (e.g., glucose) and non-analyte-related signalcomponents, while the second working electrode detects a signalcomprising only the non-analyte-related signal components. Asubstantially analyte-only signal can be determined algorithmically,such as, but not limited to, by subtracting the non-analyte-relatedsignal component (detected by the second working electrode) from thetotal signal (e.g., detected by the first working electrode), therebyproviding a substantially “noise-free” analyte signal.

FIG. 2E illustrates the continuous glucose sensor in yet anotherembodiment, a continuous glucose sensor configured for implantation intoa host's circulatory system, in fluid communication with a host'scirculatory system, and/or into an extracorporeal circulatory device. Asshown in FIG. 2E, in some embodiments, the continuous glucose sensor 12is disposed within a catheter 1201 inserted into a vein 1204 or arteryof the host. The catheter 1201 is attached to IV tubing 1203 via aconnector 1202, such as a Leur lock. In the embodiment illustrated inFIG. 2E, the sensor 12 is exposed to samples of the host's circulatorysystem (e.g., blood 1205) by withdrawing a blood sample into thecatheter lumen such that the sensing portion of the sensor is exposed tothe sample. In some alternative embodiments, the sensor 12 is disposedwithin the fluid connector or other portion of the IV tubing in fluidcommunication with the host's circulatory system. In this embodiment,after generation of a signal associated with the concentration ofglucose in the blood sample, the sample is expelled from the catheter(e.g., back into the circulatory system) and the sensor is washed andcalibrated. Additional embodiments are described in greater detail inco-pending U.S. patent application Ser. No. 11/543,396, filed Oct. 4,2006 and entitled “Analyte Sensor,” co-pending U.S. patent applicationSer. No. 12/055,114, filed Mar. 25, 2008 and entitled “Analyte Sensor,”and U.S. Patent Publication No. US-2008-0108942-A1. In an alternativeembodiment, the continuous glucose sensor comprises an intravascularsensor such as described with reference to U.S. Pat. No. 6,477,395 toSchulman et al. In another alternative embodiment, the continuousglucose sensor comprises an intravascular sensor such as described withreference to U.S. Pat. No. 6,424,847 to Mastrototaro et al. All of theabove patents and/or patent applications are incorporated in theirentirety herein by reference.

The methods and devices of preferred embodiments can be employed in acontinuous glucose sensor that measures a concentration of glucose or asubstance indicative of a concentration or a presence of glucose.However, certain methods and devices of preferred embodiments are alsosuitable for use in connection with non-continuous (e.g., single pointmeasurement or finger stick) monitors, such as the OneTouch® systemmanufactured by LifeScan, Inc., or monitors as disclosed in U.S. Pat.Nos. 5,418,142; 5,515,170; 5,526,120; 5,922,530; 5,968,836; and6,335,203. In some embodiments, the device can analyze a plurality ofintermittent biological samples, such as blood, interstitial fluid, orthe like. The glucose sensor can use any method of glucose-measurement,including colorimetric, enzymatic, chemical, physical, electrochemical,spectrophotometric, polarimetric, calorimetric, radiometric, or thelike. In alternative embodiments, the sensor can be any sensor capableof determining the level of an analyte in the body, for example oxygen,lactase, hormones, cholesterol, medicaments, viruses, or the like.

Although a few exemplary embodiments of continuous glucose sensors areillustrated and described herein, it should be understood that thedisclosed embodiments are applicable to any device capable of singleanalyte, substantially continual or continuous measurement of aconcentration of analyte of interest and providing an output signal thatrepresents the concentration of that analyte.

Medicament Delivery Device

Some preferred embodiments provide an integrated system 10, whichincludes a medicament delivery device 16 for administering a medicamentto a host 8. An integrated medicament delivery device can be designedfor bolus injection, continuous injection, inhalation, transdermalabsorption, other method for administering medicament, or anycombinations thereof. The term medicament includes any substance used intherapy for a host 8 using the system 10, for example, insulin,pramlintide, exenatide, amylin, glucagon, derivatives thereof, and thelike. PCT International Publication No. WO02/43566 describes glucose,glucagon, and vitamins A, C, or D that can be used with the preferredembodiments. U.S. Pat. Nos. 6,051,551 and 6,024,090 describe types ofinsulin suitable for inhalation that can be used with the preferredembodiments. U.S. Pat. Nos. 5,234,906, 6,319,893, and European Pat. No.760677 describe various derivatives of glucagon that can be used withthe preferred embodiments. U.S. Pat. No. 6,653,332 describes acombination therapy that can be used with the preferred embodiments.U.S. Pat. No. 6,471,689 and PCT International Publication No. WO81/01794describe insulins useful for delivery pumps that can be used with thepreferred embodiments. U.S. Pat. No. 5,226,895 describes a method ofproviding more than one type of insulin that can be used with thepreferred embodiments. All of the above patents and publications areincorporated herein by reference in their entirety and can be useful asthe medicament(s) in the preferred embodiments.

In some embodiments, the medicament delivery device is configured forinjection and/or infusion of the medicament. For example, in someembodiments, a medicament delivery device is an infusion pump, such asbut not limited to a bedside or a portable infusion pump. In oneembodiment, the infusion is a portable medicament pump, as describedelsewhere herein. In one preferred embodiment, the medicament deliverydevice 16 is a medicament pump designed for basal and/or bolus infusionof medicament. The medicament pump of the preferred embodiments includesany portable or bedside (e.g., non-portable) infusion devices, such asis appreciated by one skilled in the art. A few examples of medicamentinfusion devices (e.g., pumps) that can be used with the preferredembodiments include U.S. Pat. Nos. 5,389,078, 6,471,689, 6,656,148,6,749,587, 6,999,854, 7,060,059, 7,109,878, 7,267,665, 7,291,133,7,311,691, 7,374,556 7,303,549, PCT International Publication No. WO81/01794, European Patent No. 1281351 and co-pending U.S. patentapplication Ser. No. 12/055,114, filed Mar. 25, 3008 and entitled“Analyte Sensor,” all of which are incorporated herein by reference intheir entirety.

In some embodiments, a medicament delivery device 16 is a hand-heldmedicament injection pen, such as but not limited to a syringe,medicament injection pen or a pneumatic injection device. In someembodiments, the hand-held medicament injection pen is configured forsingle-use (e.g., disposed of after use). In other embodiments, thehand-held medicament injection pen is a multi-use injection devicehaving single-use, disposable parts. For example, a medicament injectionpen can be configured to use single-use, disposable needles that arethrown away after one use. In one exemplary embodiment, the medicamentinjection pen is configured for use with a cartridge of a plurality ofsingle-use, disposable needles, such that each used needle can bechanged and/or removed, such as but not limited to by ejecting a usedneedle and installing an unused (e.g., sterile) needle. In still otherembodiments, the hand-held medicament injection pen is a multi-usedevice configured to sequentially deliver (e.g., aseptically) medicamentdoses to each of a plurality of hosts. For example, in one embodiment,the hand-held medicament injection pen is a pneumatic injection device.

In one preferred embodiment, the integrated medicament delivery device16 is a hand-held medicament injection pen (e.g., insulin pen) designedfor bolus injection. The hand-held medicament injection pen of thepreferred embodiments includes any pen-type injector, such as isappreciated by one skilled in the art. A few examples of a hand-heldmedicament injection pens that can be used with the preferredembodiments include U.S. Pat. Nos. 4,865,591, 5,104,380, 5,226,895,5,308,340, 5,383,865, 5,536,249, 6,192,891, 7,169,132, 7,195,616,7,291,132, U.S. Patent Publication No. US-2001-0051792-A1, U.S. PatentPublication No. US-2007-0061674-A1 and U.S. Patent Publication No.US-2008-0015511-A1, each of which is incorporated herein by reference intheir entirety.

In some embodiments, a medicament delivery device (e.g., hand-heldmedicament injection pen) is provided, which includes a processor and awired or wireless connection to a receiver, which are described in moredetail elsewhere herein. In some embodiments, the device includesprogramming that receives instructions from the receiver 14 regardingtype and amount of medicament to administer. In some embodiments,wherein the medicament delivery device is an injection device (e.g., apen) that includes more than one type of medicament, the receiverprovides the necessary instructions to determine which type or types ofmedicament to administer, and can provide instructions necessary formixing the one or more medicaments. In some embodiments, the receiverprovides the glucose trend information (for example, concentration,rate-of-change, acceleration, or other user input information) and theinjection device includes programming necessary to determine appropriatemedicament delivery. In some embodiments, the receiver, user interface,and/or integrated electronics are incorporated into and/or integral withthe pen. However, any of the electronics (including hardware, firmwareand/or software/programming) associated with the receiver, medicamentdelivery device and/or optional single point monitor can be located inany one or a combination of the receiver, medicament delivery deviceand/or optional single point monitor.

In some embodiments, the receiver and/or hand-held medicament injectionpen is configured to calculate medicament usage and/or a remainingon-board medicament amount. In some embodiments, the integratedelectronics (e.g., in the receiver and/or medicament delivery device)are configured to receive sensor data and calculate an amount of timeremaining with the current medicament on-board the delivery device(e.g., the amount of medicament within the medicament device'sreservoir/cartridge) based on historic, current, estimated, and/orpredicted glucose data. In some embodiments, integrated electronicsinclude electronics associated with a receiver and a pen, which can beconfigured for two-way communication there between, such as described inmore detail elsewhere herein.

In some embodiments, the pen includes programming to send informationregarding the amount, type, and time of medicament delivery administeredto the receiver 14 for processing. The receiver 14 can use thisinformation received from the pen, in combination with the continuousglucose data obtained from the sensor, to monitor and determine thehost's glucose patterns, such as to measure his response to eachmedicament delivery. Knowing the host's individual response to each typeand amount of medicament delivery can be useful in adjusting oroptimizing the host's therapy. It is noted that individual metabolicprofiles (for example, medicament sensitivity) are variable from host tohost and time to time. While not wishing to be bound by theory, it isbelieved that once the receiver has learned (or as the receivercontinuously learns) the individual's metabolic patterns, includingglucose trends and associated medicament deliveries, the receiver can beprogrammed to adjust and optimize the therapy recommendations for thehost's individual physiology to maintain their glucose levels within adesired target range. In some embodiments, the receiver (including userinterface and integrated electronics) is integral with and/orincorporated into the pen.

In some embodiments, the receiver includes algorithms that useparameters provided by the continuous glucose sensor, such as glucoseconcentration, rate-of-change of the glucose concentration, andacceleration of the glucose concentration to more particularly determinethe type, amount, and time of medicament administration, can be appliedto the integrated system 10, such as described herein. However, theintegrated system additionally provides convenience by automation (forexample, data transfer through operable connection) and reducedopportunity for human error than may be experienced with theconventional therapy.

In some embodiments, integrated electronics, which are described in moredetail elsewhere herein, include programming that requires at least oneof the receiver 14, the single point glucose monitor 18, and thehand-held medicament injection pen 16 to be validated or confirmed byanother of the components to provide a fail safe accuracy check; inthese embodiments, the validation includes algorithms programmed intoany one or more of the components. In some embodiments, the integratedelectronics include programming that requires at least one of thereceiver 14 and the hand-held medicament injection pen 16 (e.g.,hand-held medicament injection pen such as a pen) to be validated orconfirmed by a human (for example, to confirm the amount and/or type ofmedicament). In these embodiments, validation provides a means by whichthe receiver can be used adjunctively, when the host or doctor wouldlike to have more control over the host's therapy decisions, forexample. See FIGS. 15 and 16 for exemplary processes that can beimplemented herein.

In some embodiments, the hand-held medicament injection pen 16 includesa motor configured for electronic control of at least a portion of thehand-held medicament injection pen. In some embodiments, a motor isconfigured to automatically set an amount of medicament to be deliveredto the host, such as but not limited to a medicament bolus amount, forexample, using a step motor. In some embodiments, a motor is configuredto control a rate of medicament injection into the host. In someembodiments, the integrated electronics (e.g., the receiver), describedin more detail elsewhere herein, are configured to remotely control atleast one motor, such as those described above. In some embodiments, theintegrated electronics are configured to provide a recommended therapyamount (e.g., medicament bolus amount), which can be communicated to thehand-held medicament injection pen (or which can be integral with thepen); in some such embodiments, the integrated electronics and/orhand-held medicament injection pen electronics are configured toautomatically set the bolus amount using the motor (e.g., a step motor),however, in some embodiments, a validation step can be required. In someembodiments, the integrated electronics and/or the hand-held medicamentinjection pen electronics are configured to automatically inject themedicament at a controlled speed and/or rate. Preferably, the system isconfigured to inject the medicament at an optimum rate to reduce tissuedamage and optimize the medicament absorption, which are believed toenable the effectiveness of the medicament to be more consistent overtime. In some embodiments, actuation (or control) of setting a bolusamount(s) and/or injection of the medicament is controlled by a receiveroperably connected to the hand-held medicament injection pen, forexample by actuation (or selection) of a button, a user selectable menuitem, or on a touch screen. In alternative embodiments, actuation (orcontrol) of setting a bolus amount(s) and/or injection of the medicamentis controlled by the hand-held medicament injection pen, for example byactuation (or selection) of a button, a user selectable menu item, or ona touch screen.

Although much of this description and the exemplary embodiments aredrawn to an integrated hand-held medicament injection pen, theintegration concepts described herein are applicable to a variety ofother medicament devices, including inhalation devices, transdermalpatches, and the like.

Receiver

The preferred embodiments provide an integrated system 10, whichincludes a receiver 14 that receives and processes the raw data streamfrom the continuous glucose sensor 12. The receiver can perform all orsome of the following operations: a calibration, converting sensor data,updating the calibration, evaluating received reference and sensor data,evaluating the calibration for the analyte sensor, validating receivedreference and sensor data, displaying a meaningful glucose value to auser, calculating therapy recommendations, validating recommendedtherapy, adaptive programming for learning individual metabolicpatterns, and prediction of glucose values, for example. Somecomplementary systems and methods associated with the receiver aredescribed in more detail with reference to co-pending U.S. PatentPublication No. US-2005-0027463-A1, which is incorporated herein byreference in its entirety.

In some embodiments, the receiver 14 is a PDA- or pager-sized housing,for example, and comprises a user interface 96 that has a plurality ofbuttons 108 and a liquid crystal display (LCD) screen, which can includea backlight. In some embodiments, the receiver can take other forms, forexample a hand-held medicament injection pen case, a hand-heldmedicament injection pen kit, a hand-held medicament injection penhousing, a medicament delivery device housing and/or receiver, acomputer, a server, a cell phone, a personal digital assistant (PDA), orother such device capable of receiving and processing the data such asdescribed herein. Additionally or alternatively, the user interface caninclude a keyboard, a speaker, a scroll wheel, and/or a vibrator such asdescribed with reference to FIG. 13. The receiver 14 comprises systems(for example, electronics) necessary to receive, process, and displaysensor data from the glucose sensor 12, such as described in more detailwith reference to FIG. 13. The receiver 14 processes data from thecontinuous glucose sensor 12 and additionally processes data associatedwith at least one of the hand-held medicament injection pen 16, a singlepoint glucose meter 16, and a host 8 (user).

In some embodiments, the receiver is integral with (physically connectedto) the sensor. In some embodiments, the receiver 14 is integrallyformed with a medicament delivery device 16 and/or a single pointglucose monitor 18. In some embodiments, the receiver 14, the medicamentdelivery device 16 and/or a single point glucose monitor 18 aredetachably connected, so that one or more of the components can beindividually detached and attached at the user's convenience. In someembodiments, the receiver 14, the medicament delivery device 16, and/ora single point glucose monitor 18 are separate from, detachablyconnectable to, or integral with each other; and one or more of thecomponents are operably connected through a wired or wirelessconnection, allowing data transfer and thus integration between thecomponents. In some embodiments, the receiver 14 and the medicamentdelivery device 16 (e.g., a hand-held medicament injection pen) eachcomprise mutually engaging electrical contacts, which are configured toallow communication between the hand-held medicament injection pen andthe receiver. In a further embodiment, the integrated system isconfigured to initiate communication between the receiver and thehand-held medicament injection pen, in response to engagement of theelectrical contacts. Upon engagement of the electrical contacts, thesystem is configured to communicate medicament delivery data between thereceiver and the hand-held medicament injection pen.

In some embodiments, the receiver 14 includes a housing and a userinterface 196 located on the receiver housing. In some embodiments, ahand-held medicament injection pen is provided and includes a housing,wherein the user interface 196 is located on the hand-held medicamentinjection pen housing. In some embodiments, a housing is provided,wherein the housing is configured to receive a hand-held medicamentinjection pen and wherein the housing includes a user interface 196. Insome embodiments, a hand-held medicament injection pen kit is provided,wherein the hand-held medicament injection pen kit is configured toreceive the hand-held medicament injection pen (and can be configured toreceive other accessories, such as medicament cartridges, needles, andthe like), wherein the user interface 196 is located on the hand-heldmedicament injection pen kit. In some embodiments, a receiver,integrated electronics, and a hand-held medicament injection pen areintegrally formed into one housing.

In some alternative embodiments, a flexible LED screen is provided as auser interface (or a component thereof), wherein the flexible LED screenis physically located on at least one of the receiver and the hand-heldmedicament injection pen and/or operably connected to at least one ofthe receiver and the hand-held medicament injection pen, and wherein theintegrated electronics are configured to display sensor data on theflexible LED screen.

In some alternative embodiments, an image projection system is provided,wherein the integrated electronics are configured to project data onto asurface (e.g., wall, skin, and the like) as a user interface (or acomponent thereof). For example, the image projection system can beprovided on the receiver, hand-held medicament injection pen, and/or anyhousing associated therewith, wherein the image projection system isconfigured to project an image such as alphanumeric data, icons,pictures, and the like, similar to that conventionally seen on an LCDscreen, for example. In use, the image can be projected automatically orin response to actuation by a user, wherein the image includes data suchas glucose concentration and/or glucose trend, therapy recommendations,event markers, and the like.

Single Point Glucose Monitor

In some embodiments, the integrated system is configured and arrange foroperable communication with a single point glucose monitor 18, such asbut not limited to a meter for measuring glucose within a biologicalsample, including a sensing region that has a sensing membraneimpregnated with an enzyme, similar to the sensing membrane describedwith reference to U.S. Pat. Nos. 4,994,167 and 4,757,022, which areincorporated herein in their entirety by reference. In some embodiments,the single point glucose monitor includes a conventional finger stickdevice. However, in alternative embodiments, the single point glucosemonitor can use other measurement techniques including enzymatic,chemical, physical, electrochemical, spectrophotometric, polarimetric,calorimetric, radiometric, and the like. In some embodiments, the singlepoint glucose monitor is configured for wired or wireless communicationwith a component of the integrated system (e.g., automatic and/orsemi-automatic communication), such as but not limited to the receiver.However, in other embodiments, the single point glucose monitor is notconfigured for operable communication with the integrated system, suchthat the host must manually input the single point glucose monitor data(e.g., into the receiver). It is noted that the meter is optional inthat a separate meter can be used and the glucose data downloaded orinput by a user into the receiver.

Integrated System Design

In preferred embodiments, an integrated system 10 includes a receiver 14(e.g., including user interface and integrated electronics), amedicament delivery device 16, and optionally a single point glucosemeter 18, wherein the integrated electronics are configured to processand display continuous glucose data from a continuous glucose sensor 12,including trend graphs, glucose concentration, rate of changeinformation (e.g., directional arrow(s)), high and low glucose alarms,and/or the like, on the user interface. In some embodiments, theintegrated electronics are configured to process and display informationfrom the medicament delivery device (e.g., hand-held medicamentinjection pen). The user interface and integrated electronics can beincluded in and/or on the hand-held medicament injection pen, ahand-held medicament injection pen kit, the receiver, housingsassociated therewith, and/or combinations thereof.

In some embodiments, an integrated hand-held medicament injection penkit is provided, including for example, a case configured to hold ahand-held medicament injection pen, one or more medicament cartridges,one or more needles, etc., as is appreciated by one skilled in the art.In some embodiments, the integrated hand-held medicament injection penkit additionally includes a user interface (e.g., an LCD screen), forexample on an outside (or an inside) of the case, configured to displaycontinuous glucose data such as described elsewhere herein. In theseembodiments, the kit includes electronics, operatively connected to theuser interface, including programming configured to perform all or someof the following operations: calibrating and displaying the continuousglucose sensor data, calculating therapy recommendations (e.g., using abolus-type calculator), validating (e.g., by a user) recommendedtherapy, and adaptive algorithms configured for learning individualmetabolic patterns (e.g., response to therapies administered by thepen), for example.

FIG. 3 is a perspective view of an integrated system 20 in oneembodiment, showing an LCD screen 106 on a hand-held medicamentinjection pen housing 22. In this exemplary embodiment, the hand-heldmedicament injection pen 20 includes a hand-held medicament injectionpen housing 22, a receiver, integrated electronics, and an LCD screen106, all of which are integrally formed therewith and/or incorporatedtherein. The hand-held medicament injection pen housing 22 furtherincludes a port 24 configured to receive medicament cartridges and/orneedles, and which an end cap can cover. The LCD screen 106 isconfigured to display data from the continuous glucose sensor and/or thehand-held medicament injection pen, as described in more detailelsewhere herein. An ergonomic handhold includes indentations 26configured to allow a user's fingers to rest or hold during actuation ofthe hand-held medicament injection pen via insertion button 28, forexample. While not shown, in some embodiments, sensor and/or medicamentdelivery electronics can be located partially or wholly with thereceiver, with the sensor and/or with the medicament delivery device(s).In some embodiments, the electronics are distributed between thereceiver, the sensor and/or the medicament delivery device(s).

In one exemplary embodiment the integrated system 10 is configured andarranged for monitoring and treating diabetes, and includes a medicamentdelivery device 16 configured and arranged for injecting an amount ofmedicament into a host 8 and an integrated receiver 14 configured andarranged to receive sensor data from a continuous glucose sensor 12,wherein the sensor data is indicative of a glucose concentration of thehost in vivo, wherein the integrated receiver comprises electronicsconfigured and arranged to process the sensor data. In some embodiments,the electronics are further configured to calculate an amount ofmedicament therapy (e.g., a deliverable medicament dose, such as but notlimited to a bolus dose to be delivered to the host) and/or a time ofmedicament therapy delivery. As is appreciated by one skilled in theart, the integrated electronics can be located entirely within thereceiver 14, or one or more portions of the electronics can be locatedwith the continuous glucose sensor 12 and/or the medicament deliverydevice 16 or combinations thereof. Similarly, in some embodiments, thereceiver 14 (including integrated electronics) is a separate unit fromthe sensor 12 and/or hand-held medicament injection pen 16, while inother embodiments, the receiver (in part or in whole) can be integratedwith sensor and/or hand-held medicament injection pen, as is describedin greater detail herein. For example, in some embodiments, theintegrated receiver includes a housing and the hand-held medicamentinjection pen is integrally formed with the housing.

In another exemplary embodiment, an integrated system 10 for monitoringand treating diabetes is provided, the system comprising a receiver 14configured and arranged to receive sensor data from an operablyconnected continuous glucose sensor 12, wherein the continuous glucosesensor is configured and arranged to generate sensor data associatedwith a glucose concentration of a host; integrated electronicsconfigured to process the sensor data and to generate a medicamenttherapy (e.g., insulin therapy, pramlintide therapy, exenatide therapy,combinations thereof), and an integrated hand-held medicament injectionpen 16 for injecting an amount of the corresponding medicament into thehost based at least in part on the medicament therapy. The medicamenttherapy includes but is not limited to a medicament identity, an amountof medicament therapy and/or a time of medicament therapy delivery. Insome further embodiments, the receiver and the hand-held medicamentinjection pen are integrally formed. However, in some other furtherembodiments, the receiver and hand-held medicament injection pen aredetachably connectable, as described elsewhere herein.

In a further embodiment of a detachably connectable hand-held medicamentinjection pen 16 (e.g., an insulin, pramlintide or exenatide pen) andreceiver 14 housing, the system 10 is configured to initiatecommunication between the hand-held medicament injection pen and thereceiver in response to (detachable) connection of the hand-heldmedicament injection pen and the housing. For example, in someembodiments, the hand-held medicament injection pen and the housing caninclude mutually engaging contacts (e.g., electrical contacts) that mate(e.g., make an electrical connection) when the hand-held medicamentinjection pen is connected to the housing and initiate communicationbetween the receiver and the hand-held medicament injection pen. Uponinitiation of communication, the receiver and the hand-held medicamentinjection pen can transmit data. For example, an amount of medicamenttherapy (e.g., calculated by the integrated electronics), such as butnot limited to a bolus medicament dose (e.g., an amount and type ofmedicament to be delivered), and a time of medicament therapy can becommunicated to the hand-held medicament injection pen, such that themedicament therapy can be delivered to (e.g., injected into) the host.Similarly, the hand-held medicament injection pen can communicateinformation to the receiver, such as but not limited the amount ofmedicament delivered to the host, the time the medicament was delivered,the amount of medicament remaining in the hand-held medicament injectionpen to be used, the type of medicament contained in the hand-heldmedicament injection pen, and the like. In some embodiments, wirelesscommunication between the hand-held medicament injection pen and thereceiver can be initiated by engagement of the contacts or by hostactuation of a switch, button, or the like. In some embodiments,communication between the hand-held medicament injection pen and thereceiver is initiated after connection by actuation of a switch, buttonor the like, such as by the host or by attachment of the two devices.For example, in one embodiment, when the hand-held medicament injectionpen is inserted into the receiver housing, an external surface of thehand-held medicament injection pen comes into an adjacent parallelorientation with respect to an internal surface of the receiver housing,which results in depression of a communication actuation button on theinterior of the receiver housing. One skilled in the art can appreciatealternative configurations.

In a further embodiment, the integrated system includes a user interface196, which is configured an arranged for input of host informationand/or output of sensor data and/or medicament delivery data, such as,for example, the LCD screens 106 illustrated in FIGS. 3-12. For example,the user interface can include a keyboard 198, buttons 108 and/or atouch screen for input of host information, selection from menus, andthe like. The host information includes any information related to thehost and his/her medicament therapy, such as but not limited to a hostidentification (e.g., host ID code/number), physical characteristics ofthe host, a type of medicament to be injected into the host, a targetblood glucose range/level, a protocol for the medicament therapyassigned to the host, an alert, an alarm, and the like. For example, inan embodiment useful in a clinical setting, a caretaker (e.g., nurse,doctor, physician's assistant) can enter a host's ID number and glucoseconcentration via the user interface, which enables the integratedelectronics to calculate a deliverable medicament dose (e.g., accordingto the medicament therapy protocol assigned to that host ID number),which in turn enables the nurse to deliver an appropriate bolusmedicament dose to the host at the bedside. In some embodiments, whenthe nurse is within a communication distance of the host and his/herimplanted continuous glucose sensor, the receiver is configured tointerrogate the sensor for the host information and/or sensor dataassociated with the host's glucose concentration.

In preferred embodiments, the integrated system is configured andarranged to require validation prior to injection an amount ofmedicament into the host. For example, in some embodiments, theintegrated system can prompt the user (e.g., a caretaker, such as anurse or doctor, or the host himself) to validate (e.g., verify) via theuser interface (e.g., via the speaker 100, vibrator 102 or screen) thehost ID, the host's assigned medicament therapy protocol and/or theytype of medicament on board the hand-held medicament injection pen.Additionally, the integrated system can display information to thenurse, such as the host ID, sensor data received from the continuousglucose sensor, processed sensor data, medicament delivery data (e.g.,data related to a medicament therapy to be delivered to the host), andthe like.

FIG. 4 is a perspective view of an integrated system 32 in anotherembodiment, showing an LCD screen 106 on a hand-held medicamentinjection pen housing 36. In this exemplary embodiment, the hand-heldmedicament injection pen housing 36 includes a hand-held medicamentinjection pen, a receiver, integrated electronics, and an LCD screen,all of which are integrally formed therewith and/or incorporatedtherein. The hand-held medicament injection pen housing 36 furtherincludes a port 38 configured to received medicament cartridges and/orneedles, and which an end cap can cover. The LCD screen 106 isconfigured to display data from the continuous glucose sensor and/or thehand-held medicament injection pen, as described in more detailelsewhere herein. An ergonomic handhold includes a thumb hold 40configured to allow a user's thumb to rest or hold during actuation ofthe hand-held medicament injection pen via insertion button 42, forexample. Additionally, a scroll wheel 44 (also referred to as a jogwheel, thumb wheel, jog encoder, or rotary encoder) is provided thatallows for scrolling through menus, data (e.g., numbers), and/oroptions, for example, and selection of the menus, data and/or options.In one such embodiment, the scroll wheel enables the user to view avariety of menu driven screens or options for initiating a sensor,displaying glucose data, displaying therapy recommendations, modifyingtherapy recommendations, and the like, by scrolling up or down on thewheel; additionally, the scroll wheel enables the user to select fromthe screens or options by depressing the scroll wheel. It is believedthat incorporation of a scroll wheel into the integrated system enablesa more compact system design with good ergonomics, usability, andreliability. In some embodiments, one or more buttons and/or toggles areincluded (alternatively or in addition to a scroll wheel) for movingthrough menus, data, options and the like.

FIG. 5 is a perspective view of an integrated system 46 in anotherembodiment, showing a housing 48 configured to receive a hand-heldmedicament injection pen 50 wherein the housing includes an LCD screen106 thereon. In this exemplary embodiment, the housing 48 includes areceiver, integrated electronics, and an LCD screen 106 integrallyformed therewith and/or incorporated therein. Additionally, the housingincludes an opening 54 configured to receive the hand-held medicamentinjection pen 50. The illustrated hand-held medicament injection penshows a dial 56 for setting the medicament bolus amount, a screen 58 forviewing the medicament bolus amount (e.g., from about 0 to about 70units of medicament in some embodiments) while turning the dial 56, amedicament cartridge holder/receptacle 60 and a needle 62; however, anyknown hand-held medicament injection pen configured can be used, as isappreciated by one skilled in the art, and as described in more detailelsewhere herein. In some embodiments, the integrated system includes areceptacle configured and arranged to receive and medicament cartridge,thereby medicament can be delivered to the host. In some embodiments,wherein the pen and the housing are separate, the receptacle 60 isincluded in the hand-held medicament injection pen, as illustrated inFIG. 5. However, in embodiments wherein the pen and the housing areintegrally formed, the receptacle can be integrally formed with thehousing. The integrated system is configured such that the hand-heldmedicament injection pen is at least partially received, and can besubstantially fully received by the housing 48. In some embodiments, anend cap 64 is provided to protect the end of the hand-held medicamentinjection pen and/or for with a storage compartment for storinghand-held medicament injection pen accessories (e.g., needles,medicament cartridges, and the like). The illustrated housing 48includes an LCD screen 106 and a scroll wheel 44, which are described inmore detail elsewhere herein.

In some embodiments, such as the embodiment illustrated in FIG. 5, thehand-held medicament injection pen is detachably connectable to thereceiver. In some embodiments, wherein integrated system 46 includes ahousing configured to receive the hand-held medicament injection pen,mutually engaging contacts are provided on the hand-held medicamentinjection pen and on the housing (e.g., receiver, case, etc), such thatwhen the pen is received by (detachably connected to) the housing (e.g.,in a predetermined position), direct communication between the pen andthe housing (e.g., receiver and/or integrated electronics housedtherein) can occur. In some embodiments, the integrated system isconfigured to detect when the pen is received by the housing andsubsequently upload and/or download information there between. In someembodiments, the integrated system is configured to initiatecommunication between the hand-held medicament injection pen and thehousing (e.g., receiver and/or integrated electronics) in response tomutual engagement of the electrical contacts. In some embodiments, theintegrated system is configured communicate data (e.g., recommendedmedicament bolus amount, actual amount of medicament delivered, and timeof medicament delivery, glucose data, and the like) between thehand-held medicament injection pen and the housing (e.g., receiverand/or integrated electronics) in response to engagement of theelectrical contacts.

FIG. 6 is a perspective view of an integrated system 46 in yet anotherembodiment, wherein the integrated receiver 14 includes a housing 48configured to receive a hand-held medicament injection pen 50 whereinthe housing includes an LCD screen 106 thereon. In this exemplaryembodiment, the housing 48 includes a receiver, integrated electronics,and an LCD screen 106 integrally formed therewith and/or incorporatedtherein. The illustrated hand-held medicament injection pen 50 shows ascreen 58 for viewing the medicament bolus amount, which can be selectedusing actuation button 44 located on the housing. Actuation button 44can also be used to toggle/scroll through menus on LCD screen 106. Insome embodiments, the hand-held medicament injection pen includescontacts that mate with contacts of the housing, such that theintegrated electronics can automatically set a bolus dose, such as acalculated medicament therapy, that can then be manually delivered bythe host. Accordingly, in some embodiments, the hand-held medicamentinjection pen 16 is detachably connectable to the housing. For example,the hand-held medicament injection pen can be connected to the housingand then removed/separated from the housing. For example, in someembodiments, the hand-held medicament injection pen is disposable and afirst hand-held medicament injection pen is removed and thrown away,followed by connection of a second (e.g., new, unused) hand-heldmedicament injection pen. In another example, the hand-held medicamentinjection pen is not disposable, but uses disposable cartridges ofmedicament received in a receptacle. Accordingly, in this example, thehand-held medicament injection pen can be disconnected from the housing,for medicament cartridge replacement, followed by reconnection of thepen to the housing.

FIG. 7 is a perspective view of an integrated system 46 a in yet anotherembodiment, in which the integrated receiver 14 includes a housing 48 a,such as but not limited to a hand-held medicament injection pen kit,configured to receive a hand-held medicament injection pen 50, whereinthe receiver housing includes an LCD screen 106 and an actuation button44 thereon. In this exemplary embodiment, the system is configured andarranged as a hand-held medicament injection pen kit having a two-parthousing configured to open in a clam-shell manner, with a hinge at oneedge. While the device illustrated in FIG. 7 includes top and bottomportions connected by a hinge structure, the device can include morethan two portions or the portions can be in different orientations fromthat depicted in FIG. 7. For example, in some embodiments, the housinghas three hingeably-connected portions (e.g., top, middle and bottom).In other embodiments, the portions could open from side to side or fromfront to back, or any combination thereof. In still other embodiments, aportion of the housing is removably connected (e.g., a batterycompartment cover) or is configured to slide/pop out of the housing,such as a drawer.

In the illustrated embodiment (FIG. 7), the receiver housing isconfigured with a top portion including a user interface 196 (e.g., theLCD screen 106 (e.g., for display of sensor data and/or the medicamenttherapy) and an actuation button 44) located thereon, and a bottomportion configured with compartments 50 a and 60 a configured to hold(e.g., store) the hand-held medicament injection pen 50 as well as oneor more accessories (e.g., medicament cartridges, needles, alcoholwipes, etc.). In some embodiments, display a representation ofmedicament delivery on the user interface, wherein the representation ofmedicament delivery is substantially adjacent to substantiallytime-corresponding sensor data, such at that described elsewhere withreference to FIG. 14. In some embodiments, the user interface includes aflexible LED screen operably connected to at least one of the receiverand the hand-held medicament injection pen, such as, for example, afold-out or unrolling flexible screen that can be folded up and/orrolled up for storage when not in use. Accordingly, the integratedelectronics are configured to display continuous glucose sensor data onthe flexible LED screen. In other embodiments, the user interfaceincludes an image projection system configured to project continuousglucose sensor data onto a surface, such as but not limited to a wall, atable top, a book, and the like.

In some embodiments, such as the illustrated embodiment FIG. 7, thehand-held medicament injection pen is detachably connectable to thereceiver housing. For example, the hand-held medicament injection penand the recess for receiving the hand-held medicament injection pen caninclude mutually engaging electrical contacts that engage when thehand-held medicament injection pen is put away in the housing. Similarlyto the hand-held medicament injection pen, in some embodiments, thereceiver is connected to the housing (either detachably ornon-detachably). However, in preferred embodiments, the receiver (e.g.,including integrated electronics) is integrally formed with the housing.In some embodiments, the system is configured to initiate communicationbetween the hand-held medicament injection pen and the receiver inresponse to engagement of the mutually engaging electrical contacts(e.g., when the pen is put away in the housing), such thatdata/information (e.g., the medicament therapy) can be communicatedbetween the receiver and hand-held medicament injection pen. The housingincludes the receiver and integrated electronics, as well as a connector48 b, for connection of a power cable (e.g., to re-charge an includedbattery) and/or a data cable (e.g., for connection to a single-pointglucose monitor for calibration and/or for connection to a computer,such as for data transfer and/or battery charging). In some embodiments,the hand-held medicament injection pen (e.g., motorized) and theinterior of the housing comprise mutually engaging contacts, whereby,when the pen is installed in the housing and the pen and housingcontacts are engaged, the integrated electronics can set a bolus dose(on the pen) to be delivered to the host.

FIG. 8 is a perspective view of an integrated system 66 in anotherembodiment, showing a hand-held medicament injection pen housing 68, areceiver, integrated electronics, a user interface and a hand-heldmedicament injection pen integrally formed and/or incorporated therein.The hand-held medicament injection pen housing 68 further includes aport 70 configured to received medicament cartridges and/or needles, andwhich an end cap can cover. The LCD screen 106 is configured to displaydata from the continuous glucose sensor and/or the hand-held medicamentinjection pen, as described in more detail elsewhere herein. Anergonomic handhold includes an indentation 72 configured to allow auser's index finger to rest or hold during actuation of the hand-heldmedicament injection pen via an insertion button 74, for example.

FIG. 9 is a perspective view of an integrated system 76 in anotherembodiment, showing a receiver housing 78 including a receiver,integrated electronics, a user interface and a hand-held medicamentinjection pen integrally formed therewith and/or incorporated therein.An actuation button 80 (e.g., for actuation of the hand-held medicamentinjection pen) is incorporated into the integrated receiver housing; thereceiver housing further includes a port on an opposing side (e.g., tothe actuation button, not shown in FIG. 9) configured to receivemedicament cartridges and/or needles, and which an end cap can cover. Insome embodiments, the hand-held medicament injection pen is integrallyformed with and/or incorporated into the receiver housing; however,alternative embodiments include an opening in the receiver housingconfigured to receive a hand-held medicament injection pen similar tothat illustrated in FIG. 5 (e.g., such that is detachably connectablethereto). The LCD screen 106 is configured to display data from thecontinuous glucose sensor and/or the hand-held medicament injection pen,as described in more detail elsewhere herein. The illustrated housingfurther includes a scroll wheel 44, which is described in more detailelsewhere herein. It is believed that the illustrated configuration ofFIG. 9 enables a low profile device, wherein a user can wear or carrythe integrated system discretely.

FIG. 10 is a perspective view of an integrated system 82 in anotherembodiment, showing a receiver housing 84 including a receiver,integrated electronics, a user interface, and a hand-held medicamentinjection pen integrally formed therewith and/or incorporated therein.The illustrated embodiment of FIG. 10 is substantially similar to FIG.9; however the integrated hand-held medicament injection pen is rotated90 degrees within the design of the housing.

FIG. 11 is a perspective view of an integrated system 80 showing anintegrated housing 88 including a receiver, integrated electronics, auser interface, and a hand-held medicament injection pen, wherein thehousing further includes a cap for the hand-held medicament injectionpen. This illustrated embodiment is similar to that of FIGS. 6 and 7,however further includes a cap 90 configured to protect the end of thehand-held medicament injection pen and/or for with a storage compartmentfor storing hand-held medicament injection pen accessories (e.g.,needles, medicament cartridges, and the like).

FIG. 12 is a perspective view of an integrated system 92 showing anintegrated housing 94 including a receiver, integrated electronics, auser interface, and a hand-held medicament injection pen, wherein thehousing further includes a cap for the hand-held medicament injectionpen. This illustrated embodiment is similar to that of FIG. 11, howeverincludes a hinged end cap 96 and can enable a design with a reducedvolume/size to encourage patient acceptance and/or use.

Integrated Electronics

FIG. 13 is a block diagram that illustrates integrated systemelectronics in one embodiment. One embodiment is described wherein theprocessor within the receiver performs much of the processing, howeverit is understood that all or some of the programming and processingdescribed herein can be accomplished within the continuous glucosesensor, the receiver, a single point glucose monitor, and/or thedelivery device, or any combination thereof. Similarly, displays, alarmsand other user interface functions can be incorporated into any of theindividual components of the integrated delivery device.

In some embodiments, the receiver includes a housing with integratedelectronics located within the receiver housing. In some embodiments, ahand-held medicament injection pen comprises a housing, and wherein theintegrated electronics are located within the hand-held medicamentinjection pen housing. In some embodiments, a housing is configured toreceive a hand-held medicament injection pen, wherein the housingincludes integrated electronics therein. In some embodiments, ahand-held medicament injection pen kit is provided, wherein thehand-held medicament injection pen kit is configured to receive thehand-held medicament injection pen (and can be configured to receiveother accessories, such as medicament cartridges, needles, and thelike), wherein the integrated electronics are located within thehand-held medicament injection pen kit. In some embodiments, a receiver,integrated electronics and hand-held medicament injection pen areintegrally formed into one housing.

A quartz crystal 176 is operably connected to an RF transceiver 178 thattogether function to receive and synchronize data streams via an antenna180 (for example, transmission 140). Once received, a processor module182 processes the signals, such as described below. However othermethods of wired or wireless communication can be substituted for the RFcommunication described herein.

The processor (or processor module) 182 is the central control unit thatperforms the processing, such as storing data, analyzing a continuousglucose sensor data stream, analyzing single point glucose values,accuracy checking, checking clinical acceptability, calibrating sensordata, downloading data, recommending therapy instructions, calculatingmedicament delivery amount, type and time, learning individual metabolicpatterns, and controlling the user interface, by providing prompts,messages, warnings and alarms, and the like. The processor (or processormodule) can include hardware and software that performs the processingdescribed herein, including for example, read only memory (ROM), such asflash memory, provides permanent or semi-permanent storage of data,storing data such as sensor ID, receiver ID, and programming to processdata streams (for example, programming for performing estimation andother algorithms described elsewhere herein), and random access memory(RAM) stores the system's cache memory and is helpful in dataprocessing.

In some embodiments, the processor 182 monitors the continuous glucosesensor data stream 140 to determine a preferable time for capturingglucose concentration values, using the single point glucose monitorelectronics 116 for calibration of the continuous sensor data stream.For example, when sensor glucose data (for example, observed from thedata stream) changes too rapidly, a single point glucose monitor readingmay not be sufficiently reliable for calibration during unstable glucosechanges in the host; in contrast, when sensor glucose data arerelatively stable (for example, relatively low rate of change), a singlepoint glucose monitor reading can be taken for a reliable calibration.In some additional embodiments, the processor can prompt the user viathe user interface to obtain a single point glucose value forcalibration at predetermined intervals. In some additional embodiments,the user interface can prompt the user to obtain a single point glucosemonitor value for calibration based upon certain events, such as meals,exercise, large excursions in glucose levels, faulty or interrupted datareadings, and the like. In some embodiments, certain acceptabilityparameters can be set for reference values received from the singlepoint glucose monitor. For example, in one embodiment, the receiver onlyaccepts reference glucose data between about 40 and about 400 mg/dL.

In some embodiments, the processor 182 monitors the continuous glucosesensor data to determine a preferable time for medicament delivery,including type, amount, and time. In some embodiments, the processor isprogrammed to detect impending clinical risk and can request data input,a reference glucose value from the single point glucose monitor, and thelike, in order to confirm a therapy recommendation. In some embodiments,the processor is programmed to process continuous glucose data andmedicament therapies, to adaptively adjust to an individual's metabolicpatterns. In some embodiments, the processor is programmed to projectglucose trends based on data from the integrated system (for example,medicament delivery information, user input, and the like). In someembodiments, the processor is programmed to calibrate the continuousglucose sensor based on the integrated single point glucose monitor 18.Numerous other programming can be incorporated into the processor, as isappreciated by one skilled in the art, as is described in cited patentsand patent applications here, and as is described with reference toflowcharts of FIGS. 15 and 16.

A battery 192 is operably connected to the processor 182 and providespower for the receiver. In one embodiment, the battery is a standard AAAalkaline battery, however any appropriately sized and powered batterycan be used. In some embodiments, a plurality of batteries can be usedto power the system. In some embodiments, a power port (not shown) isprovided permit recharging of rechargeable batteries. A quartz crystal194 is operably connected to the processor 182 and maintains system timefor the computer system as a whole.

A PC communication (com) port 190 can be provided to enablecommunication with systems, for example, a serial communications port,allows for communicating with another computer system (for example, PC,PDA, server, or the like). In one exemplary embodiment, the receiver isconfigured to download historical data to a physician's PC forretrospective analysis by the physician. The PC communication port 190can also be used to interface with other medical devices, for examplepacemakers, implanted analyte sensor patches, infusion devices,telemetry devices, and the like.

A user interface 196 includes a keyboard 198, a speaker 100, a vibrator102, a backlight 104, a liquid crystal display (LCD) 106, one or morebuttons 108, and/or a scroll wheel 44 (shown in FIG. 4, for example).The components that comprise the user interface 196 provide controls tointeract with the user. The keyboard 198 can allow, for example, inputof user information about himself/herself, such as mealtime, exercise,medicament administration, and reference glucose values. The speaker 100can provide, for example, audible signals or alerts for conditions suchas present and/or predicted hyper- and hypoglycemic conditions. Thevibrator 102 can provide, for example, tactile signals or alerts forreasons such as described with reference to the speaker, above. Thebacklight 104 can be provided, for example, to aid the user in readingthe LCD in low light conditions. The LCD 106 can be provided, forexample, to provide the user with visual data output. In someembodiments, the LCD is a touch-activated screen. The buttons 108 and/orscroll wheel 44 (see FIGS. 4 and 6, for example) can provide for toggle,menu selection, option selection, mode selection, and reset, forexample. In some alternative embodiments, a microphone can be providedto allow for voice-activated control.

The user interface 196, which is operably connected to the processor182, serves to provide data input and output for both the continuousglucose sensor, the hand-held medicament injection pen, and/or for thesingle point glucose monitor. Data output includes a numeric estimatedanalyte value, an indication of directional trend of analyteconcentration, a graphical representation of the measured analyte dataover a period of time, alarms/alerts, therapy recommendations, actualtherapy administered, event markers, and the like. In some embodiments,the integrated electronics are configured to display a representation ofa target glucose value or target glucose range on the user interface.Some additional data representations are disclosed in Published U.S.Patent Application No. 2005-0203360, which is incorporated herein byreference in its entirety

FIG. 14 is a graphical representation of integrated data that can bedisplayed on an LCD screen 106, for example, in one embodiment. In thisembodiment, the integrated electronics are configured to display arepresentation of a value of the sensor data (illustrated by bars inthis illustration) above or below the target glucose value (illustratedby a line at “145” (mg/dL) in FIG. 14) or target glucose range (notshown) on the user interface. In the illustrated embodiment, the x-axisrepresents time and the y-axis represents glucose concentration inmg/dL. Glucose concentration is graphed over time according to its valueas compared to a target (e.g., above and/or below the target). Forexample, if a target glucose concentration is set at 145 mg/dL and theactual glucose concentration is 180 mg/dL, then the bar value represents35 mg/dL (180 mg/dL-145 mg/dL) above the target glucose concentrationfor that glucose measurement. While FIG. 14 shows the glucoseconcentration as a series of black bars, the data can be shown using avariety of symbols. For example, in one embodiment, the bars arecolored, with green bars above the target and red bars below the target.In another embodiment using colored bars, the bars are colored as agradient, wherein the bars within the target range are green, changingto yellow and then red as the host's glucose concentration is fartherand farther away from the target range. In another embodiment, dots,circles, squares and the like are used instead of bars. In still anotherembodiment, stars, hearts, a thumbs-up graphic, and/or smiley-faces(colored and/or black and white) can be added to the graph to denoteperiods of time during which the host was within the target. In afurther embodiment, the stars, hearts, a thumbs-up graphic, and/orsmiley-faces can blink or flash as an award for staying within thetarget. In still another embodiment, instead of using colors, portionsof the graph are made to blink/flash. For example, in one embodiment, aseries of dots plot out the host's glucose concentration, with the mostrecent concentration blinking.

In some embodiments, the integrated electronics are configured todisplay a representation of medicament delivery on the user interfaceadjacent to substantially time-corresponding sensor data, which isillustrated as “10 U” and “7 U” in FIG. 14, representing the units ofmedicament delivered in a bolus. In these embodiments, therepresentation of medicament delivery is located substantially adjacentto a glucose value measured at substantially the same time as themedicament delivery. It is believed that by providing a representationof medicament delivery on the user adjacent to substantiallytime-corresponding sensor data, a user can see the affect of the therapy(e.g., medicament bolus) on their glucose concentration and/orachievement of target glucose concentration.

In some embodiments, the integrated electronics are configured todisplay glucose data on the user interface for 1 hour, 3 hours, 6 hours,9 hours, 1 day, 3 days, 5 days, 7 days, 1 month, 3 months, year-to-date,1 year, 2 years, 5 years, and the like for example, which provides theuser with actual, averaged or estimated glucose values over that timeperiod. In some embodiments, the integrated electronics are configuredto display glucose trend data (e.g., charts or graphs) on the userinterface, including a graphical representation of glucose values asthey change over time. In some embodiments, the integrated electronicsare configured to display comparison data for two periods (e.g., chartsor graphs) on the user interface, including a trend-related findingbetween two specific periods of time. In some embodiments, theintegrated electronics are configured to display modal day data (e.g.,charts or graphs) on the user interface, including glucose summary databased on mealtimes. In some embodiments, the integrated electronics areconfigured to display modal week data (e.g., charts or graphs) on theuser interface, including glucose summary data based on days of theweek. In some embodiments, the integrated electronics are configured todisplay medicament dosage and effects data (e.g., charts or graphs) onthe user interface, including medicament regimen information and changesin base medicament pattern. In some embodiments, the integratedelectronics are configured to display hypoglycemia and hyperglycemiaepisode data (e.g., charts or graphs) on the user interface, includinginformation regarding very low and very high glucose readings and/orglucose readings outside of a target range (which can be defined by theuser in some embodiments). In some embodiments, the integratedelectronics are configured to display rapid swings data (e.g., charts orgraphs) on the user interface, including incidents of rapid swingsbetween low and high blood glucose levels, which levels can bepre-programmed or settable by a user, for example.

In some embodiments, prompts or messages can be displayed on the userinterface to convey information to the user, such as malfunction,outlier values, missed data transmissions, or the like, for thecontinuous glucose sensor. Additionally, prompts can be displayed toguide the user through calibration of the continuous glucose sensor.Even more, calibrated sensor glucose data can be displayed, which isdescribed in more detail with reference to co-pending U.S. PatentPublication No. US-2005-0027463-A1 and U.S. Patent Publication No.US-2005-0203360-A1, each of which is incorporated herein by reference intheir entirety.

In some embodiments, prompts or messages about the hand-held medicamentinjection pen can be displayed on the user interface to inform orconfirm to the user type, amount, and time of medicament delivery. Insome embodiments, the user interface provides historical data andanalytes pattern information about the medicament delivery, and thehost's metabolic response to that delivery, which may be useful to apatient or doctor in determining the level of effect of variousmedicaments.

Referring again to FIG. 13, electronics 110 associated with the deliverydevice 16 are operably connected to the processor 182 and include aprocessor 112 for processing data associated with the delivery device 16and include at least a wired or wireless connection 114 for transmissionof data between the processor 182 of the receiver 14 and the processormodule 112 of the delivery device 16. In some embodiments, the deliverydevice electronics 110 are at least partially or fully incorporated intothe integrated electronics, such that electronics 110 may not berequired. Other electronics associated with any of the delivery devicescited herein, or other known delivery devices, can be implemented withthe delivery device electronics 110 described herein, as is appreciatedby one skilled in the art.

In some embodiments, the processor module 112 comprises programming forprocessing the delivery information in combination with the continuoussensor information. In some alternative embodiments, the processor 182comprises programming for processing the delivery information incombination with the continuous sensor information. In some embodiments,both processors 182 and 112 mutually process information related to eachcomponent.

In some embodiments, the hand-held medicament injection pen 16 furtherincludes a user interface (not shown), which can include a displayand/or buttons, for example. U.S. Pat. Nos. 6,192,891, 5,536,249, and6,471,689 describe some examples of incorporation of a user interfaceinto a hand-held medicament injection pen, as is appreciated by oneskilled in the art.

Electronics 116 associated with the optional single point glucosemonitor 18 are operably connected to the processor module 120 andinclude a potentiostat 118, in one embodiment, that measures a currentflow produced at the working electrode when a biological sample isplaced on the sensing membrane, such as described above.

Algorithms

FIG. 15 is a flow chart that illustrates the process 230 of validatingtherapy instructions prior to medicament delivery, in one embodiment. Insome embodiments, the system is configured with programming thatprovides for validation of therapy recommendations. In some embodiments,the therapy recommendations include a suggestion, on the user interface,of time, amount, and type of medicament to delivery. In someembodiments, therapy instructions include calculating a time, an amount,and/or a type of medicament delivery to administer, and optionallytransmitting those instructions to the delivery device. In someembodiments, therapy instructions include that portion of a closed loopsystem wherein the determination and delivery of medicament isaccomplished, as is appreciated by one skilled in the art.

In some embodiments, the therapy recommendations are displayed on a userinterface (e.g., of an integrated housing) by representative icons, suchas a syringe, a medicament pen, a medicament pump, an apple, orangejuice, candy bar, or any icon representative of eating, drinking, oradministering therapy, for example. Additionally or alternatively, thetherapy recommendations can be preset alphanumeric messages, forexample, “3.0 Units,” “consume carbohydrates,” “inject medicament” or“no therapy required”, and can include brand names, amounts, times,acronyms, codes and the like. In response to the recommendation oftherapy displayed on the user interface, the user can confirm, modify,and/or cancel the recommended therapy, after which, the integratedhand-held medicament injection pen is configured to administer theappropriate therapy.

Although computing and processing of data is increasingly complex andreliable, there are circumstances in which the therapy recommendationsnecessitate human intervention. Some examples include when a user isabout to alter his/her metabolic state, for example due to a behaviorsuch as exercise, meal, pending manual medicament delivery, and thelike. In such examples, the therapy recommendations determined by theprogramming may not have considered present or upcoming behavior, whichcan change the recommended therapy. Numerous such circumstances canoccur, such that a validation can be advantageous in order to ensurethat therapy recommendations are appropriately administered.

At block 232, a sensor data receiving module, also referred to as thesensor data module, receives sensor data (e.g., a data stream),including one or more time-spaced sensor data points, from a sensor viathe receiver, which can be in wired or wireless communication with thesensor. The sensor data point(s) can be raw or smoothed, such asdescribed in U.S. Patent Publication No. US-2005-0043598-A1, which isincorporated herein by reference in its entirety.

At block 234, a medicament calculation module, which is a part of aprocessor module, calculates a recommended medicament therapy based onthe received sensor data. A variety of algorithms can be used tocalculate a recommended therapy as is appreciated by one skilled in theart.

At block 236, a validation module, which is a part of the processormodule, optionally validates the recommended therapy. The validation caninclude a request, from the user or another component of the integratedsystem 10, for additional data to ensure safe and accurate medicamentrecommendation or delivery. In some embodiments, the validation modulerequests and/or considers additional input, such as time of day, meals,sleep, calories, exercise, sickness, or the like. In some embodiments,the validation module is configured to request this information from theuser. In some embodiments, the validation module is responsive to a userinputting such information.

In some embodiments, when the integrated system 10 is in a fullyautomated mode, the validation module is triggered when a potential riskis evaluated. For example, when a clinically risky discrepancy isevaluated, when the acceleration of the glucose value is changing or islow (indicative of a significant change in glucose trend), when it isnear a normal meal, exercise or sleep time, when a medicament deliveryis expected based on an individual's dosing patterns, and/or a varietyof other such situations, wherein outside influences (meal time,exercise, regular medicament delivery, or the like) may requireadditional consideration in the therapy instructions. These conditionsfor triggering the validation module can be pre-programmed and/or can belearned over time, for example, as the processor module monitors andpatterns an individual's behavior patterns.

In some embodiments, the system can be programmed to request additionalinformation from the user regarding outside influences unknown to theintegrated system prior to validation. For example, exercise, food ormedicament intake, rest, and the like can be input into the receiver forincorporation into a parameter of the programming (algorithms) thatprocesses the therapy recommendations.

At block 238, the receiver confirms and sends (for example, displays,transmits and/or delivers) the therapy recommendations. In someembodiments, the receiver can simply confirm and display the recommendedtherapy, for example. In some embodiments, the receiver can confirm,transmit, and optionally deliver instructions, to the delivery device,regarding the recommended therapy, for example. In some embodiments, thereceiver can confirm and ensure the delivery of the recommended therapy,for example. In some embodiments, a glucose value measured by the singlepoint glucose monitor is used to validate the therapy recommendation. Itis noted that these examples are not meant to be limiting and there area variety of methods by which the receiver can confirm, display,transmit, and/or deliver the recommended therapy, within the scope ofthe preferred embodiments.

FIG. 16 is a flow chart 240 that illustrates the process of providingadaptive metabolic control using an integrated system, in oneembodiment. In this embodiment, the integrated system is programmed tolearn the patterns of the individual's metabolisms, including metabolicresponse to medicament delivery.

In some embodiments, the system is configured with programming thatprovides therapy recommendations based on at least one of the following:glucose concentration, glucose trend information (e.g., rate of change,acceleration, etc), predicted glucose values, food intake (e.g.,carbohydrates), exercise, illness, sleep, time of day, and the like. Inone such example, the system is configured to request carbohydrate andexercise information, from the user, which is used in combination withdata from the continuous glucose sensor to calculate a recommended doseof medicament for injection (e.g., with a hand-held medicament injectionpen). In some embodiments, when the user's glucose concentration fallsoutside of a target range (or is predicted to fall outside of a targetrange), a recommended therapy is displayed on the user interface (e.g.,of an integrated pen as described above), wherein the user has anopportunity to validate the therapy recommendation prior to injection ofmedicament. After the user has injected the medicament, the amount (andtype, etc) of medicament, which is stored in the integrated system, isanalyzed, in combination with the user's metabolic response (i.e.,continuous glucose data) over a predetermine time period (e.g., minutesto hours after injection), to determine whether the amount (and/or type)of medicament administered affected a desired change (e.g., glucoseconcentration within a target range). Preferably, the system'sprogramming is configured to process the medicament delivery informationand the continuous glucose sensor information, to adaptively adjusttherapy recommendations to an individual's metabolic patterns. Namely,with each medicament injection and/or over multiple medicamentinjections, the system is configured to adaptively learn how a userresponds to various therapies and to adaptively adjust the calculationof therapy recommendations accordingly.

At block 242, a medicament data receiving module, which can beprogrammed within the receiver 14 and/or medicament delivery device 16,receives medicament delivery data, including time, amount, and/or type.In some embodiments, the user is prompted to input medicament deliveryinformation into the user interface. In some embodiments, the medicamentdelivery device 16 sends the medicament delivery data to the medicamentdata-receiving module.

At block 244, a sensor data receiving module, also referred to as thesensor data module, receives sensor data (e.g., a data stream),including one or more time-spaced sensor data points, from a sensor viathe receiver, which can be in wired or wireless communication with thesensor.

At block 246, the processor module, which can be programmed into thereceiver 14 and/or the delivery device 16, is programmed to monitor thesensor data from the sensor data module 242 and medicament delivery datafrom the medicament delivery module 244 to determine an individual'smetabolic profile, including their response to various times, amounts,and/or types of medicaments. The processor module can use any patternrecognition-type algorithm, as is appreciated by one skilled in the art,to quantify the individual's metabolic profile.

At block 248, a medicament calculation module, which is a part of aprocessor module, calculates the recommended medicament based on thesensor glucose data, medicament delivery data, and/or the host'sindividual's metabolic profile. In some embodiments, the recommendedtherapy is validated such as described with reference to FIG. 15, above.In some embodiments, the recommended therapy is manually,semi-automatically, or automatically delivered to the host.

At block 250, the process of monitoring and evaluation a host'smetabolic profile is repeated with each receipt of new medicamentdelivery data, wherein the processor monitors the sensor data and theassociated medicament delivery data to determine the individual'smetabolic response, in order to adaptively adjust to newly determinedmetabolic profile or patterns, if necessary. This process can becontinuous throughout the life of the integrated system, can beinitiated based on conditions met by the continuous glucose sensor, canbe triggered by a patient or doctor, and/or can be provided during astart-up or learning phase.

While not wishing to be bound by theory, it is believed that byadaptively adjusting the medicament delivery based on an individual'smetabolic profile, including response to medicaments, improved long-termpatient care and overall health can be achieved.

Integrated Systems for Clinical Settings

FIG. 17 is a block diagram illustrating an integrated diabetesmonitoring and treatment system for use in a clinical setting, in oneembodiment. The integrated system includes a continuous glucose sensor12 configured to continuously detect a signal associated with a glucoseconcentration of a host, a processor module 182 configured and arrangedto process the signal to generate sensor data and a therapy instruction,wherein the therapy instruction comprises a deliverable medicament dosein some embodiments, and a communication module 1700 configured andarranged to communicate the therapy instruction between the processormodule and a medicament delivery device 16, such as one or morehand-held medicament injection pens. Although much of the description isrelated to hand-held medicament injection pens, the preferredembodiments can be applied to any such medicament delivery deviceconfigured for bolus therapy, such as medicament inhalers, and/or thelike. In one exemplary embodiment, the glucose sensor is implanted in ahost. In some embodiments, a processor module 182 associated with thesensor, processes the sensor data to calculate and medicament therapy(e.g., a medicament dose to be delivered to the host) and acommunication module 1700 communicates the medicament therapyinstruction to the hand-held medicament injection pen 16, such as butnot limited to via wireless communication. In some embodiments, theprocessor continually calculates a deliverable medicament dose that canbe transmitted to a hand-held medicament injection pen within range ofthe communication module. In other embodiments, the processor modulecalculates the medicament therapy in response to interrogation by ahand-held medicament injection pen, such as via wireless communication.For example, a caretaker can use a hand-held medicament injection pen 16to interrogate the patient's continuous glucose sensor 12, to receivethe medicament therapy instruction (e.g., identification of the host anda deliverable medicament dose calculated by the processor module 182;communicated to the hand-held medicament injection pen by thecommunication module 1700). In some preferred embodiments, thecontinuous glucose sensor includes the processor module configured todetermine a medicament therapy instruction. However, in someembodiments, the system is configured such that at least a portion ofthe processor module is disposed within the hand-held medicamentinjection pen, such that the medicament device performs at least some ofthe calculations to generate the medicament therapy instruction. In someembodiments, the continuous glucose sensor includes only the minimalelectronics necessary to collect the sensor data and (optionally)process the collected data into a data packet that is then communicatedto the hand-held medicament injection pen, wherein the hand-heldmedicament injection pen includes a processor module and processes thedata received to generate the medicament therapy instruction. Variousintermediate configurations can be appreciated by one skilled in theart.

After receiving the medicament therapy instruction, the caretaker candeliver the medicament dose to the patient, simply by actuating themedicament injection pen. As shown in FIG. 17, the continuous glucosesensor 12 is configured and arranged to communicate with a plurality ofhand-held medicament injection pens (16 n), such that in a clinicalsetting, such as a hospital, each caretaker can carry a hand-heldmedicament injection pen and use that hand-held medicament injection pento deliver medicament to the patient (host) as a part of the normalcourse of patient care, similar to the practice of measuring thepatient's temperature, pulse, blood pressure, respiration, pO₂, urineoutput, and the like, at regular intervals as determined by hospitalprotocol.

In preferred embodiments, the processor module 182 includes an inputmodule configured for the input of host information and/or a therapyinstruction. Preferably, the device is configured and arranged to beprogrammed (e.g., operated) by an external programmer, such as acaretaker. Such information can be input into the device when thecontinuous glucose sensor 12 is implanted in the host. For example, insome embodiments, the input module is configured to receive informationfrom a user interface, a hand-held medicament injection pen, an infusionpump, a patient monitor, a single-point glucose monitor, a receiver, andthe like. In some embodiments, the information can be input via a userinterface incorporated into the continuous glucose sensor or via thehand-held medicament injection pen, which can include a user interface.In other embodiments, the information can be input via a tertiary devicehaving a user interface and configured for communication with thecommunication module, such as but not limited to a computer, patientmonitor, PDA and the like.

In preferred embodiments, host information that can be input via aninput module associated with the continuous glucose sensor and/or thehand-held medicament injection pen, wherein the host informationincludes but is not limited to a host ID, such as a unique identifyingcode assigned to a patient, host physical characteristics, a type ofmedicament to be delivered to the host, a therapy protocol assigned tothe host, and the like. A therapy instruction includes but is notlimited to selection of a therapy protocol and/or portions thereof,including but not limited to a target host blood glucose concentrationand/or range of concentrations, selection of an alert to be sounded ifthe host meets a predetermined criterion, and the like. In preferredembodiments, the therapy instruction comprises at least one of a type ofmedicament, a medicament dose, and a delivery time. The integratedelectronics are further configured and arranged to process hostinformation and/or a therapy instruction. For example, the integratedelectronics can process the continuous glucose sensor data in thecontext of a selected protocol, such that medicament therapies arecalculated to maintain the host within a target blood glucoseconcentration range (e.g., 100-140 mg/dl blood glucose), for example. Inpreferred embodiments, the device includes a display module configuredand arranged for display of the host information, sensor data, thetherapy instruction, the deliverable medicament dose, an alert and/or analarm.

In some embodiments, the system is configured for communication with adata repository system and/or device (e.g., portable and/or remotelylocated) configured to receive host information, sensor data, thetherapy instruction, the deliverable medicament dose, an alert, analarm, a predictive alarm, and the like. For example, in someembodiments, the communication module is configured to transmitinformation related to the host and his/her treatment to a datarepository that records and tracks the host's condition and/or entersthe data into the host's patient chart. For example, the data can beelectronically entered into the host's patient chart remotely, such asin medical records. In another embodiment, the information can bemonitored remotely by the patient's physician using a data repositorydevice integrated into a display device, such as a personal computer,cell phone, PDA and the like, which enables the physician to receivepredictive alarms of upcoming problems/events or alarms/alerts relatedto the host's current physical state. Similarly, when the physicianvisits the host, he can use a portable data repository to collectpertinent data from the continuous glucose sensor. In one exemplaryembodiment, the continuous glucose sensor is configured to communicatedata and information related to the medicament therapy to a separateand/or remote data repository, for example, wherein the sensor isconfigured to transmit this information to a remote monitor carried bythe physician or at the nurse's station, or to a remote location (e.g.,medical records) for storage and/or monitoring. In another exemplaryembodiment, the hand-held medicament injection pen (e.g., insulin pen)is configured to communicate data received from the continuous glucosesensor (e.g., via the communication module) and information related tomedicament therapy delivered to the host to the separate and/or remotedata repository, for example, by transmitting this information to aremote monitor carried by the physician or at the nurse's station, or toa remote location (e.g., medical records) for storage and/or monitoring.

As shown in FIG. 17, the integrated system includes a hand-heldmedicament injection pen 16, configured to communicate with thecontinuous glucose sensor 12 (e.g., and vice versa) and to deliver amedicament to the host. In some embodiments, the system is configured tocommunicate with a plurality of hand-held medicament injection pens 16n. For example, in one embodiment, the system is configured such that ahost wearing a continuous glucose sensor can be monitored and/or treatedby a plurality of caretakers, each of whom carries a hand-heldmedicament injection pen. For example, the host's sensor is configuredto communicate with a first caretaker's hand-held medicament injectionpen, then a second caretaker's hand-held medicament injection pen, andso on. As a non-limiting example, for a host in the hospital, at theinitiation of each work shift, a new nurse can check the host's glucoselevel (e.g., via communication between the host's sensor and the nurse'shand-held medicament injection pen, as described herein) and deliverinsulin, if needed. Accordingly, the continuous glucose sensor and thehand-held medicament injection pen(s) can communicate with each otherwhen operably connected, to allow wired and/or wireless communicationtherebetween.

FIG. 18 is a block diagram illustrating a medicament delivery device formonitoring and treating diabetes in one or more host, such as but notlimited to in a clinical setting, in another embodiment. Although muchof the description is related to hand-held medicament injection pens,the preferred embodiments can be applied to any such medicament deliverydevice configured for bolus therapy, such as medicament inhalers, and/orthe like. The medicament delivery device 16 includes a communicationmodule 1700 configured to interrogate an operably connected continuousglucose sensor 12 and to receive sensor data (e.g., a signal associatedwith a glucose concentration of a host) therefrom, a processor module182 configured to process the sensor data and calculate a medicamenttherapy, and a hand-held medicament injection pen (e.g., configured toreceive a cartridge of medicament for injection) configured and arrangedto deliver medicament based at least in part on the medicament therapy.In some embodiments, the system is configured for use with a continuousglucose sensor configured and arranged for transcutaneous implantationin the host, such as for use in the general wards, in which case thesignal generated by the glucose sensor can be measured in theinterstitial fluid, for example. In other embodiments, the system isconfigured for use with a continuous glucose sensor configured andarranged for implantation in the host's circulatory system (e.g., via anartery or vein) or in an extracorporeal blood circulation device, inwhich case the signal generated by the glucose sensor is associated witha glucose concentration of a sample of the host's circulatory system.

In one embodiment, the communication module 1700, which can beintegrally formed with the hand-held medicament injection pen or inwired or wireless communication therewith or detachably connected to thehand-held medicament injection pen, is configured to receive informationfrom an operably connected continuous glucose sensor when the hand-heldmedicament injection pen interrogates it. The hand-held medicamentinjection pen and the continuous glucose sensor can be operablyconnected using any method known in the art, such as but not limited toby wired and/or wireless communication. In one embodiment, the caretakercan simply hold the hand-held medicament injection pen within apredetermined communication range, such that the hand-held medicamentinjection pen and continuous glucose sensor can communicate with eachother by wireless communication, such as RF, IR, Bluetooth, and thelike. In another embodiment, the system is configured such that thehand-held medicament injection pen can communicate with the sensor viainductive coupling communication when the caretaker holds the penadjacent to the sensor or touches the pen to the sensor. A variety ofalternative useful communication methodologies are appreciated by oneskilled in the art.

In some embodiments, the hand-held medicament injection pen 16 includesa processor module 182 that includes programming for calculating themedicament therapy based at least in part on the sensor data, asdescribed elsewhere herein. For example, the programming directs use ofalgorithms for calculating an amount of medicament to be delivered tothe host, based at least in part on the sensor data received from thehost's continuous glucose sensor. In preferred embodiments, theprocessor module calculates dosing information (e.g., a type ofmedicament to be delivered, an amount of medicament to be delivered anda time of delivery, and/or the like) using one or more algorithmsdescribed elsewhere herein. While the embodiment shown in FIG. 18depicts the processor module 182 disposed within the hand-heldmedicament injection pen, in some embodiments, some or all of theprocessor electronics and/or functions can reside within the continuousanalyte sensor(s) 12 n. For example, in some embodiments, theelectronics/components/modules (e.g., processor module, communicationmodule, and the like) of receiver 14, as depicted in FIG. 18, can bedistributed among other integrated system components, such as but notlimited to the continuous analyte sensor 12 and the hand-held medicamentinjection pen.

In some embodiments, the processor module 182 is configured forvalidation of the dosing information. For example, the processor modulecan request validation of a calculated medicament dose and/oridentification of the host prior to injection of the dose into the host.In some embodiments, the system is configured to disallow/preventinjection unless at least the dose (e.g., medicament identity, amount ofmedicament to be delivered and/or time of delivery) and/or hostinformation has been validated. For example, the hand-held medicamentinjection pen can interrogate a first continuous glucose sensor,calculate a medicament dose and request validation prior to allowing thecaretaker to inject the calculated dose into the host. The caretaker canmove on to a second host and repeat the process. Accordingly, accidentalinjection (e.g., of one host's medicament dose into another host) can beavoided.

Preferably, the hand-held medicament injection pen includes a userinterface, such as that described with reference to FIG. 13, configuredand arranged for input and/or display of at least some medicalinformation, wherein medical information comprises at least one of hostinformation, received sensor data, processed sensor data, the calculatedmedicament therapy, a delivered medicament therapy, an instruction, analert, an alarm and a failsafe. Host information includes at least oneof a host ID, type of medicament to be received, a target glucose leveland/or range, predicted hypoglycemia/hypoglycemia, a therapy protocol,an alert, and an alarm. In some embodiments, the user interface isdetachably connected to the hand-held medicament injection pen, such asvia mutually engaging contacts that allow communication therebetweenthen the user interface is connected with the hand-held medicamentinjection pen. However, in other embodiments, the user interface (inpart or in its entirety) is integrally formed with the hand-heldmedicament injection pen.

In some embodiments, the hand-held medicament injection pen includes acommunication module 1700 configured to communicate treatmentinformation (e.g., host information, continuous glucose information, thetherapy protocol, dosing information, medicament type, medicamentdelivered and time of medicament delivery) to a central monitor. Acentral monitor can be a device configured to receive informationcommunicated from one or more hand-held medicament injection pens, suchas a computerized device including a user interface for display ofreceived information and optionally for communicatingcommands/instructions back to one or more hand-held medicament injectionpens. In some embodiments, a central monitor can include one or moreintermediate receiving devices, located about the hospital ward or atthe nurses' station, and configured to receive the communicatedinformation wirelessly, and then to relay the communicated informationto the central monitor via a wired and/or wireless connection. In someembodiments, the system can be configured such that when a caretakermoves within a range of the intermediate receiving device and/or thecentral monitor itself, the receiving device/central monitor recognizesthe hand-held medicament injection pen and triggers the pen to downloadinformation related to treatment of the host(s). Alternatively,recognition of the receiving device/central monitor by the hand-heldmedicament injection pen triggers the information download. The centralmonitor can be located in a centralized location, such as at the nurses'station or in medical records, or in a more private remote location,such as in the physician's office or in a nurse supervisor's office.Location of the central monitor at a location remote from the glucosesensor(s) and/or hand-held medicament injection pen enables remotemonitoring of hand-held medicament injection pen use (e.g., how, when &where it is used) and/or function (e.g., if it is functioning properly).

In some embodiments, at least a portion of the system is configuredprovide adaptive metabolic control of the host's glucose, as describedwith reference to FIG. 16. Accordingly, the processor module isconfigured to receive sensor data and medicament therapy data (e.g.,information related to medicament delivery to the host) and to monitorthe sensor data for the host's metabolic response to the deliveredmedicament therapy. Accordingly, the system can calculate new medicamenttherapy based on the host's metabolic response to the medicamentdeliver. For example, if the host is highly sensitive to insulin, thesystem can intelligently monitor the host's response to an insulin doseand recalculate new medicament doses to take the host's insulinsensitivity into account. For example, in this particular circumstance,the processor module can calculate a small insulin dose, such that thehost's glucose is maintained within the target range and hypoglycemiacan be avoided. In another example, a host may be very insensitive toinsulin. In the case of this insulin insensitive host, the system canmonitor the lack of glucose concentration decreases upon insulin therapydelivery, and re-calculate future insulin doses (e.g., increase thevolume of insulin delivered in a bolus dose and/or increase a basaldelivery rate), such that this host's glucose can be maintained in thetarget range.

Integrated Systems for Ambulatory Use

FIG. 19 is a block diagram illustrating an integrated system (monitoringand treating diabetes) for ambulatory use, in one embodiment. Such asystem can be used by an ambulatory host to accurately monitor and treathis diabetes in real-time, by continuously monitoring his blood glucoselevel and infusing/injecting medicament with a basal medicament deliverydevice (e.g., a medicament pump) and a bolus medicament delivery device(e.g., a hand-held medicament injection pen) based at least in part onthe data generated by the continuous glucose sensor, in either anopen-loop, closed-loop or semi-closed-loop manner. In this embodiment,the integrated system includes a receiver 14 configured and arranged toreceive continuous glucose sensor data from an operably connectedcontinuous glucose sensor 12 implanted in a host, a processor moduleconfigured to process the continuous glucose sensor data and to providemedicament dosing information based at least in part on the continuousglucose sensor data, and a communication module configured and arrangedto communicate the medicament dosing information with the medicamentdelivery devices 16 a and 16 b. Although a separate receiver isillustrated in FIG. 19, the receiver 14, including the processor moduleand/or communication module, can be located with the continuous glucosesensor, the basal medicament delivery device, the bolus medicamentdelivery device and/or combinations thereof, eliminating a need for aseparately housed receiver.

In some embodiments, the basal medicament delivery device 16 a is amedicament pump 16 a, and the medicament dosing information comprises abasal dose of medicament. Accordingly, the processor module comprisesprogramming to calculate the basal dose based at least in part on thecontinuous glucose sensor data. The receiver is configured tocommunicate the basal dose to the medicament pump, which, in turn, isconfigured to infuse the basal medicament dose into the host. Since theglucose sensor is a continuous glucose sensor, the system can beconfigured to continually recalculate the basal medicament dose andreadjust the dose according to the host's needs, as indicated by thesensor data generated by the continuous glucose sensor. This enablesadaptive metabolic control 240, as described with reference to FIG. 16,and optimized, real-time patient care.

In some preferred embodiments, the bolus medicament delivery device 16 bis a hand-held medicament injection pen 16 b and the medicament dosinginformation comprises a bolus medicament dose. Accordingly, theprocessor module comprises programming to calculate a bolus dose ofmedicament based at least in part on the continuous glucose sensor data.In some embodiments, the hand-held medicament injection pen isconfigured to infuse the same medicament as the medicament pump, whilein other embodiments, the hand-held medicament injection pen isconfigured to infuse a medicament other than the medicament infused bythe medicament pump, as is described in greater detail below. In someembodiments, the hand-held medicament injection pen includes a motor.The motor can be configured to automatically set the amount ofmedicament based at least in part on the medicament dosing information.For example the medicament dosing information can include an instructionfor the hand-held medicament injection pen to automatically portion outa bolus medicament dose, which can be manually delivered by the host. Ina further embodiment, the medicament is not delivered manually (e.g., bythe host actuating a plunger to inject the medicament), rather themedicament is delivered semi-automatically, such that the host can holdthe pen against the injection site (e.g., as if to inject themedicament) and actuate the pen to inject the medicament automatically.In this embodiment, the motor of the hand-held medicament injection pencan be configured to control a rate of medicament injection into thehost and the medicament dosing information comprises an instruction forthe hand-held medicament injection pen to deliver the bolus dose at aprogrammed rate. For example, it is known that the activity of injectedmedicament is dependent, in part, on the rate of injection. Thehand-held medicament injection pen can be configured to inject themedicament at a rate selected to optimize the medicament's activity.Accordingly, the host's management of his blood sugar can be optimizedand more consistent.

In some embodiments, the integrated system is configured for use with atleast two hand-held medicament injection pens, such as both a medicamentpump 16 a and a hand-held medicament injection pen 16 b. While the hostmay choose to use a single type of medicament in both devices, theconvenient use of multiple modes of medicament delivery is enabled bythis embodiment. For example, a first medicament delivery pump can beconfigured to deliver a first type of medicament, a second hand-heldmedicament injection pen can be configured to deliver a second type ofmedicament, and so on. In one exemplary embodiment, a medicament pump 16a is configured to deliver a long-acting medicament while a hand-heldmedicament injection pen 16 b is configured to deliver a short-actingmedicament. In a second exemplary embodiment, a medicament pump 16 a isconfigured to deliver the short-acting medicament while a hand-heldmedicament injection pen 16 b is configured to deliver the long-actingmedicament. In a third exemplary embodiment, the two medicament deliverydevices are configured to deliver the same type of medicament. Forexample, a basal medicament delivery device 16 a can be configured tofrequently deliver small doses (e.g., basal doses) of a short-actinginsulin while a bolus medicament delivery device 16 b can be configuredto deliver a large dose (e.g., a bolus) of the short-acting insulin.Additional configurations are contemplated in the preferred embodiments.Regardless, of the type of medicament delivered and the delivery deviceused, the processor module includes programming to calculate the dose ofthat particular medicament in response to the continuous glucose sensordata, such that the host can be maintained within a target blood glucoserange.

In preferred embodiments, the communication module is configured andarranged for wireless communication with the integrated hand-heldmedicament injection pen(s) 16 a/16 b, as described elsewhere herein. Insome embodiments, the communication module comprises a transceiverconfigured and arranged to interrogate and/or provide medicament dosinginformation to the integrated hand-held medicament injection pen,however, other modes of wireless communication can be used. Preferably,the communication module is configured and arranged to enablecommunicate between the at least two integrated medicament deliverydevices, such as but not limited to a medicament pump and a hand-heldmedicament injection pen. However, the use of additional hand-heldmedicament injection pens (e.g., a pump and two pens) is contemplated inthe preferred embodiments. Preferably, in preferred embodiments, thecommunication module is configured and arranged to communicate with theat least two integrated medicament delivery devices simultaneously, forexample, within substantially the same time period. Accordingly, theprocessor module calculates both the basal and bolus therapyrecommendations for the devices, respectively, considering both thebasal and bolus therapies together, and wherein the communication moduleis configured to communicate with the basal and bolus medicamentdelivery devices(s), such as to optimize control of the host's bloodglucose level, such as maintaining the host's glucose level within atarget range. In some embodiments, the communication module isconfigured to provide notification to the user, relating to injection ofthe medicament. For example, in some embodiments, the communicationmodule can alert the host (e.g., via the receiver or one of thehand-held medicament injection pens) that a medicament dose isrecommended, is being injected and/or has been injected, and optionallyrequire validation of the medicament dose, as described elsewhereherein. For example, in one embodiment, the receiver and/or hand-heldmedicament injection pen is configured to emit an auditory alert (e.g.,beep or buzz) when a bolus medicament dose have been calculated and isready to be delivered.

In preferred embodiments, the integrated system includes a userinterface configured and arranged to display continuous glucose sensordata and/or medicament dosing information. In some embodiments, the userinterface is further configured for input of host information and/ormedicament delivery device information, wherein the medicament deliverydevice information is associated with a medicament pump and a hand-heldmedicament injection pen. As described elsewhere herein, the hostinformation can include at least one of host identity, host physicalstate, target glucose concentration and type of medicament to bedelivered, and the like. Also described elsewhere herein, the medicamentdelivery information can include at least one of host identity,identification of a functionally connected hand-held medicamentinjection pen, a type of medicament to be delivered, a medicamentdelivery profile and/or protocols and a failsafe, and the like.

In one example, the host can use an integrated system including acontinuous glucose sensor 12 (e.g., a sensor as described with referenceto FIGS. 2B-2D), a receiver 14, a medicament infusion pump 16 a and ahand-held medicament injection pen 16 b, wherein the receiver isconfigured and arranged for wireless communication with the sensor, themedicament pump and the hand-held medicament injection pen. The receiverincludes a user interface that is configured such that the host canprogram the system, such as using a toggle button and/or scroll wheel toselect instructions on a display integrated into the receiver. In someembodiments, the receiver is integral with or detachably connected toeither the medicament pump or the hand-held medicament injection pen(see FIGS. 3-12), such that the host is required to carry only the pumpand the pen (e.g., instead of three devices; a receiver, a pump and apen). In some embodiments, a medicament injection pen kit is provided,as described with reference to FIGS. 6-7. Preferably, the system isconfigured such that the host can program the medicament pump to deliverbasal medicament doses and the hand-held medicament injection pen todeliver bolus medicament doses, all of which are based at least in parton sensor data generated by and received from the continuous glucosesensor, whereby the processor module processes the received sensor data,calculates the medicament doses (basal and/or bolus) and coordinates thedelivery of the medicament doses to the host. For example, the processormodule can calculate the basal medicament doses and automaticallyinstruct the medicament pump to infuse the basal doses into the host(based at least in part on the continuous glucose sensor data).Substantially simultaneously, the processor module can calculate bolusmedicament doses and set the hand-held medicament injection pen todeliver the calculated bolus dose, and then alert the host to inject thebolus dose. Advantageously, the host is afforded greater control andflexibility in managing his blood sugar, which, in turn, enablesincreased host health and reduced complication of his diabetes.

Methods and devices that are suitable for use in conjunction withaspects of the preferred embodiments are disclosed in U.S. Pat. Nos.4,994,167; 4,757,022; 6,001,067; 6,741,877; 6,702,857; 6,558,321;6,931,327; 6,862,465; 7,074,307; 7,081,195; 7,108,778; 7,110,803;7,192,450; 7,226,978; 7,310,544; 7,364,592; and 7,366,556.

Methods and devices that are suitable for use in conjunction withaspects of the preferred embodiments are disclosed in U.S. PatentPublication No. US-2005-0143635-A1; U.S. Patent Publication No.US-2005-0181012-A1; U.S. Patent Publication No. US-2005-0177036-A1; U.S.Patent Publication No. US-2005-0124873-A1; U.S. Patent Publication No.US-2005-0115832-A1; U.S. Patent Publication No. US-2005-0245799-A1; U.S.Patent Publication No. US-2005-0245795-A1; U.S. Patent Publication No.US-2005-0242479-A1; U.S. Patent Publication No. US-2005-0182451-A1; U.S.Patent Publication No. US-2005-0056552-A1; U.S. Patent Publication No.US-2005-0192557-A1; U.S. Patent Publication No. US-2005-0154271-A1; U.S.Patent Publication No. US-2004-0199059-A1; U.S. Patent Publication No.US-2005-0054909-A1; U.S. Patent Publication No. US-2005-0051427-A1; U.S.Patent Publication No. US-2003-0032874-A1; U.S. Patent Publication No.US-2005-0103625-A1; U.S. Patent Publication No. US-2005-0203360-A1; U.S.Patent Publication No. US-2005-0090607-A1; U.S. Patent Publication No.US-2005-0187720-A1; U.S. Patent Publication No. US-2005-0161346-A1; U.S.Patent Publication No. US-2006-0015020-A1; U.S. Patent Publication No.US-2005-0043598-A1; U.S. Patent Publication No. US-2005-0033132-A1; U.S.Patent Publication No. US-2005-0031689-A1; U.S. Patent Publication No.US-2004-0186362-A1; U.S. Patent Publication No. US-2005-0027463-A1; U.S.Patent Publication No. US-2005-0027181-A1; U.S. Patent Publication No.US-2005-0027180-A1; U.S. Patent Publication No. US-2006-0020187-A1; U.S.Patent Publication No. US-2006-0036142-A1; U.S. Patent Publication No.US-2006-0020192-A1; U.S. Patent Publication No. US-2006-0036143-A1; U.S.Patent Publication No. US-2006-0036140-A1; U.S. Patent Publication No.US-2006-0019327-A1; U.S. Patent Publication No. US-2006-0020186-A1; U.S.Patent Publication No. US-2006-0036139-A1; U.S. Patent Publication No.US-2006-0020191-A1; U.S. Patent Publication No. US-2006-0020188-A1; U.S.Patent Publication No. US-2006-0036141-A1; U.S. Patent Publication No.US-2006-0020190-A1; U.S. Patent Publication No. US-2006-0036145-A1; U.S.Patent Publication No. US-2006-0036144-A1; U.S. Patent Publication No.US-2006-0016700-A1; U.S. Patent Publication No. US-2006-0142651-A1; U.S.Patent Publication No. US-2006-0086624-A1; U.S. Patent Publication No.US-2006-0068208-A1; U.S. Patent Publication No. US-2006-0040402-A1; U.S.Patent Publication No. US-2006-0036142-A1; U.S. Patent Publication No.US-2006-0036141-A1; U.S. Patent Publication No. US-2006-0036143-A1; U.S.Patent Publication No. US-2006-0036140-A1; U.S. Patent Publication No.US-2006-0036139-A1; U.S. Patent Publication No. US-2006-0142651-A1; U.S.Patent Publication No. US-2006-0036145-A1; U.S. Patent Publication No.US-2006-0036144-A1; U.S. Patent Publication No. US-2006-0200022-A1; U.S.Patent Publication No. US-2006-0198864-A1; U.S. Patent Publication No.US-2006-0200019-A1; U.S. Patent Publication No. US-2006-0189856-A1; U.S.Patent Publication No. US-2006-0200020-A1; U.S. Patent Publication No.US-2006-0200970-A1; U.S. Patent Publication No. US-2006-0183984-A1; U.S.Patent Publication No. US-2006-0183985-A1; U.S. Patent Publication No.US-2006-0195029-A1; U.S. Patent Publication No. US-2006-0229512-A1; U.S.Patent Publication No. US-2006-0222566-A1; U.S. Patent Publication No.US-2007-0032706-A1; U.S. Patent Publication No. US-2007-0016381-A1; U.S.Patent Publication No. US-2007-0027370-A1; U.S. Patent Publication No.US-2007-0027384-A1; U.S. Patent Publication No. US-2007-0032718-A1; U.S.Patent Publication No. US-2007-0059196-A1; U.S. Patent Publication No.US-2007-0066873-A1; U.S. Patent Publication No. US-2007-0093704-A1; U.S.Patent Publication No. US-2007-0197890-A1; U.S. Patent Publication No.US-2007-0173710-A1; U.S. Patent Publication No. US-2007-0163880-A1; U.S.Patent Publication No. US-2007-0203966-A1; U.S. Patent Publication No.US-2007-0213611-A1; U.S. Patent Publication No. US-2007-0232879-A1; U.S.Patent Publication No. US-2007-0235331-A1; U.S. Patent Publication No.US-2008-0021666-A1; U.S. Patent Publication No. US-2008-0033254-A1; U.S.Patent Publication No. US-2008-0045824-A1; U.S. Patent Publication No.US-2008-0071156-A1; U.S. Patent Publication No. US-2008-0086042-A1; U.S.Patent Publication No. US-2008-0086044-A1; U.S. Patent Publication No.US-2008-0086273-A1; U.S. Patent Publication No. US-2008-0083617-A1; U.S.Patent Publication No. US-2008-0119703-A1; and U.S. Patent PublicationNo. US-2008-0119706-A1.

Methods and devices that are suitable for use in conjunction withaspects of the preferred embodiments are disclosed in U.S. patentapplication Ser. No. 09/447,227 filed Nov. 22, 1999 and entitled “DEVICEAND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. patent application Ser.No. 11/654,135 filed Jan. 17, 2007 and entitled “POROUS MEMBRANES FORUSE WITH IMPLANTABLE DEVICES”; U.S. patent application Ser. No.11/654,140 filed Jan. 17, 2007 and entitled “MEMBRANES FOR AN ANALYTESENSOR”; U.S. patent application Ser. No. 11/543,490 filed Oct. 4, 2006and entitled “ANALYTE SENSOR”; U.S. patent application Ser. No.11/691,426 filed Mar. 26, 2007 and entitled “ANALYTE SENSOR”; U.S.patent application Ser. No. 12/037,830 filed Feb. 26, 2008 and entitled“ANALYTE MEASURING DEVICE”; U.S. patent application Ser. No. 12/037,812filed Feb. 26, 2008 and entitled “ANALYTE MEASURING DEVICE”; U.S. patentapplication Ser. No. 12/102,654 filed Apr. 14, 2008 and entitled “SYSTEMAND METHODS FOR PROCESSING ANALYTE SENSOR DATA”; U.S. patent applicationSer. No. 12/102,729 filed Apr. 14, 2008 and entitled “SYSTEM AND METHODSFOR PROCESSING ANALYTE SENSOR DATA”; U.S. patent application Ser. No.12/102,745 filed Apr. 14, 2008 and entitled “SYSTEM AND METHODS FORPROCESSING ANALYTE SENSOR DATA”; U.S. patent application Ser. No.12/098,359 filed Apr. 4, 2008 and entitled “SYSTEM AND METHODS FORPROCESSING ANALYTE SENSOR DATA”; U.S. patent application Ser. No.12/098,353 filed Apr. 4, 2008 and entitled “SYSTEM AND METHODS FORPROCESSING ANALYTE SENSOR DATA”; U.S. patent application Ser. No.12/098,627 filed Apr. 7, 2008 and entitled “SYSTEM AND METHODS FORPROCESSING ANALYTE SENSOR DATA”; U.S. patent application Ser. No.12/103,594 filed Apr. 15, 2008 and entitled “BIOINTERFACE WITH MACRO-AND MICRO-ARCHITECTURE”; U.S. patent application Ser. No. 12/111,062filed Apr. 28, 2008 and entitled “DUAL ELECTRODE SYSTEM FOR A CONTINUOUSANALYTE SENSOR”; U.S. patent application Ser. No. 12/105,227 filed Apr.17, 2008 and entitled “TRANSCUTANEOUS MEDICAL DEVICE WITH VARIABLESTIFFNESS”; U.S. patent application Ser. No. 12/101,810 filed Apr. 11,2008 and entitled “TRANSCUTANEOUS ANALYTE SENSOR”; U.S. patentapplication Ser. No. 12/101,790 filed Apr. 11, 2008 and entitled“TRANSCUTANEOUS ANALYTE SENSOR”; U.S. patent application Ser. No.12/101,806 filed Apr. 11, 2008 and entitled “TRANSCUTANEOUS ANALYTESENSOR”; U.S. patent application Ser. No. 12/113,724 filed May 1, 2008and entitled “LOW OXYGEN IN VIVO ANALYTE SENSOR”; U.S. patentapplication Ser. No. 12/113,508 filed May 1, 2008 and entitled “LOWOXYGEN IN VIVO ANALYTE SENSOR”; U.S. patent application Ser. No.12/055,098 filed Mar. 25, 2008 and entitled “ANALYTE SENSOR”; U.S.patent application Ser. No. 12/054,953 filed Mar. 25, 2008 and entitled“ANALYTE SENSOR”; U.S. patent application Ser. No. 12/055,114 filed Mar.25, 2008 and entitled “ANALYTE SENSOR”; U.S. patent application Ser. No.12/055,078 filed Mar. 25, 2008 and entitled “ANALYTE SENSOR”; U.S.patent application Ser. No. 12/055,149 filed Mar. 25, 2008 and entitled“ANALYTE SENSOR”; U.S. patent application Ser. No. 12/055,203 filed Mar.25, 2008 and entitled “ANALYTE SENSOR”; and U.S. patent application Ser.No. 12/055,227 filed Mar. 25, 2008 and entitled “ANALYTE SENSOR”.

All references cited herein, including but not limited to published andunpublished applications, patents, and literature references, areincorporated herein by reference in their entirety and are hereby made apart of this specification. To the extent publications and patents orpatent applications incorporated by reference contradict the disclosurecontained in the specification, the specification is intended tosupersede and/or take precedence over any such contradictory material.

The term “comprising” as used herein is synonymous with “including,”“containing,” or “characterized by,” and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps.

All numbers expressing quantities of ingredients, reaction conditions,and so forth used in the specification are to be understood as beingmodified in all instances by the term “about.” Accordingly, unlessindicated to the contrary, the numerical parameters set forth herein areapproximations that may vary depending upon the desired propertiessought to be obtained. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of anyclaims in any application claiming priority to the present application,each numerical parameter should be construed in light of the number ofsignificant digits and ordinary rounding approaches.

The above description discloses several methods and materials of thepresent invention. This invention is susceptible to modifications in themethods and materials, as well as alterations in the fabrication methodsand equipment. Such modifications will become apparent to those skilledin the art from a consideration of this disclosure or practice of theinvention disclosed herein. Consequently, it is not intended that thisinvention be limited to the specific embodiments disclosed herein, butthat it cover all modifications and alternatives coming within the truescope and spirit of the invention.

What is claimed is:
 1. A system for monitoring and treating diabetes,the system comprising: a medicament injection device configured andarranged for injecting an amount of a medicament into a host; a receivermodule within the medicament injection device configured and arranged toreceive sensor data from a continuous glucose sensor, wherein the sensordata is indicative of a glucose concentration of the host in vivo,wherein the receiver module comprises electronics configured andarranged to process the sensor data to calculate at least one of a timeof medicament therapy and an amount of medicament therapy, and furthercomprising a processor within the receiver module configured andarranged to evaluate if a potential risk is present, and to requirevalidation of the calculated at least one of time of medicament therapyand amount of medicament therapy if the evaluation is that a potentialrisk is present, prior to injecting an amount of medicament into thehost, and a user interface configured and arranged for at least input ofhost information, wherein the user interface is further configured todisplay a graphical representation of at least sensor data andmedicament delivery data, wherein the user interface further displays atleast one of a target glucose concentration or a range.
 2. The system ofclaim 1, wherein the receiver module is configured to communicate in atleast one of wiredly with a single-point glucose monitor and wirelesslywith a single-point glucose monitor.
 3. The system of claim 1, whereinthe medicament injection device comprises a motor.
 4. The system ofclaim 3, wherein the motor is configured to set the amount ofmedicament.
 5. The system of claim 3, wherein the motor is configured tocontrol a rate of medicament injection into a host.
 6. The system ofclaim 3, wherein the receiver module is configured to control the motor.7. The system of claim 1, further comprising a medicament cartridgewithin the medicament injection device.
 8. A system for monitoring andtreating diabetes, the system comprising: a receiver module configuredand arranged to receive sensor data from an operably connectedcontinuous glucose sensor, wherein the continuous glucose sensor isconfigured and arranged to generate sensor data associated with aglucose concentration of a host, wherein the receiver module includes auser interface configured and arranged for at least input of hostinformation, wherein the user interface is further configured to displaya graphical representation of at least sensor data and medicamentdelivery data, wherein the user interface further displays at least oneof a target glucose concentration or a range; electronics configured toprocess the sensor data and to generate a medicament therapy, includingto calculate at least one of time of medicament therapy and amount ofmedicament therapy, and wherein the electronics are further configuredand arranged to require validation of the calculated at least one oftime of medicament therapy and amount of medicament therapy, when anevaluation step determines a potential risk is present, prior toinjecting an amount of medicament into the host; and a medicamentinjection device configured to inject an amount of medicament into thehost.
 9. The system of claim 8, further comprising a remote monitor insignal communication with the receiver module, the remote monitorconfigured to display data from the receiver module.
 10. The system ofclaim 9, wherein the remote monitor is a cell phone.
 11. The system ofclaim 10, wherein the receiver module is configured to communicate datareceived from a continuous glucose sensor and information related tomedicament therapy delivered to the host by transmitting thisinformation to the remote monitor.
 12. The system of claim 8, whereinthe receiver module is a cell phone.
 13. The system of claim 8, whereinthe processing of the sensor data is performed by software within thereceiver module.